Biomimetic peptide self-assembly for functional materials

Abstract

Natural biomolecular systems have evolved to form a rich variety of supramolecular materials and machinery fundamental to cellular function. The assembly of these structures commonly involves interactions between specific molecular building blocks, a strategy that can also be replicated in an artificial setting to prepare functional materials. The self-assembly of synthetic biomimetic peptides thus allows the exploration of chemical and sequence space beyond that used routinely by biology. In this Review, we discuss recent conceptual and experimental advances in self-assembling artificial peptidic materials. In particular, we explore how naturally occurring structures and phenomena have inspired the development of functional biomimetic materials that we can harness for potential interactions with biological systems. As our fundamental understanding of peptide self-assembly evolves, increasingly sophisticated materials and applications emerge and lead to the development of a new set of building blocks and assembly principles relevant to materials science, molecular biology, nanotechnology and precision medicine.

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Fig. 1: Supramolecular chemical space accessible to biomimetic self-assembling peptides.
Fig. 2: Biomimetic supramolecular peptide scaffolds enable cell adhesion and proliferation.
Fig. 3: Self-assembly of membrane and surfactant-like peptides at interfaces.
Fig. 4: Self-assembling biomimetic-peptide-based antimicrobial nanostructures.
Fig. 5: Mechanisms of liquid–liquid phase separation and condensation.
Fig. 6: Peptides as biomineralization scaffolds and organic–inorganic composite agents.

References

  1. 1.

    Whitesides, G. M. & Grzybowski, B. Self-assembly at all scales. Science 295, 2418–2421 (2002).

    CAS  PubMed  Google Scholar 

  2. 2.

    Philp, D. & Stoddart, J. F. Self-assembly in natural and unnatural systems. Angew. Chem. Int. Ed. Engl. 35, 1154–1196 (1996).

    Google Scholar 

  3. 3.

    Schliwa, M. & Woehlke, G. Molecular motors. Nature 422, 759–765 (2003).

    CAS  PubMed  Google Scholar 

  4. 4.

    Lehn, J. M. Perspectives in supramolecular chemistry — from molecular recognition towards molecular information processing and self-organization. Angew. Chem. Int. Ed. Engl. 29, 1304–1319 (1990).

    Google Scholar 

  5. 5.

    Aida, T., Meijer, E. W. & Stupp, S. I. Functional supramolecular polymers. Science 335, 813–817 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Zhang, S. Fabrication of novel biomaterials through molecular self-assembly. Nat. Biotechnol. 21, 1171–1178 (2003).

    CAS  PubMed  Google Scholar 

  7. 7.

    Granger, E., McNee, G., Allan, V. & Woodman, P. The role of the cytoskeleton and molecular motors in endosomal dynamics. Semin. Cell Dev. Biol. 31, 20–29 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Ananthakrishnan, R. & Ehrlicher, A. The forces behind cell movement. Int. J. Biol. Sci. 3, 303–317 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Krause, M. & Gautreau, A. Steering cell migration: lamellipodium dynamics and the regulation of directional persistence. Nat. Rev. Mol. Cell Biol. 15, 577–590 (2014).

    CAS  PubMed  Google Scholar 

  10. 10.

    Pegoraro, A. F., Janmey, P. & Weitz, D. A. Mechanical properties of the cytoskeleton and cells. Cold Spring Harb. Perspect. Biol. 9, a022038 (2017).

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Broedersz, C. P. et al. Cross-link-governed dynamics of biopolymer networks. Phys. Rev. Lett. 105, 238101 (2010).

    PubMed  Google Scholar 

  12. 12.

    Knowles, T. P. J. & Buehler, M. J. Nanomechanics of functional and pathological amyloid materials. Nat. Nanotechnol. 6, 469–479 (2011).

    CAS  PubMed  Google Scholar 

  13. 13.

    Cohen, S. I. A., Vendruscolo, M., Dobson, C. M. & Knowles, T. P. J. From macroscopic measurements to microscopic mechanisms of protein aggregation. J. Mol. Biol. 421, 160–171 (2012).

    CAS  PubMed  Google Scholar 

  14. 14.

    Oosawa, F. & Kasai, M. A theory of linear and helical aggregations of macromolecules. J. Mol. Biol. 4, 10–21 (1962).

    CAS  PubMed  Google Scholar 

  15. 15.

    Aguzzi, A. & Calella, A. M. Prions: protein aggregation and infectious diseases. Physiol. Rev. 89, 1105–1152 (2009).

    CAS  PubMed  Google Scholar 

  16. 16.

    Reches, M. & Gazit, E. Self-assembly of peptide nanotubes and amyloid-like structures by charged-termini-capped diphenylalanine peptide analogues. Isr. J. Chem. 45, 363–371 (2005).

    CAS  Google Scholar 

  17. 17.

    Sunde, M. & Blake, C. C. F. From the globular to the fibrous state: protein structure and structural conversion in amyloid formation. Q. Rev. Biophys. 31, 1–39 (1998).

    CAS  PubMed  Google Scholar 

  18. 18.

    Zhang, S., Holmes, T., Lockshin, C. & Rich, A. Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane. Proc. Natl Acad. Sci. USA 90, 3334–3338 (1993).

    CAS  PubMed  Google Scholar 

  19. 19.

    Zhang, S. et al. Self-complementary oligopeptide matrices support mammalian cell attachment. Biomaterials 16, 1385–1393 (1995).

    PubMed  Google Scholar 

  20. 20.

    Mendes, A. C., Baran, E. T., Reis, R. L. & Azevedo, H. S. Self-assembly in nature: using the principles of nature to create complex nanobiomaterials. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 5, 582–612 (2013).

    CAS  PubMed  Google Scholar 

  21. 21.

    Bromley, E. H. C., Channon, K., Moutevelis, E. & Woolfson, D. N. Peptide and protein building blocks for synthetic biology: from programming biomolecules to self-organized biomolecular systems. ACS Chem. Biol. 3, 38–50 (2008).

    CAS  PubMed  Google Scholar 

  22. 22.

    Wei, G. et al. Self-assembling peptide and protein amyloids: from structure to tailored function in nanotechnology. Chem. Soc. Rev. 46, 4661–4708 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Gazit, E. A possible role for π-stacking in the self-assembly of amyloid fibrils. FASEB J. 16, 77–83 (2002).

    CAS  PubMed  Google Scholar 

  24. 24.

    Reches, M. & Gazit, E. Designed aromatic homo-dipeptides: formation of ordered nanostructures and potential nanotechnological applications. Phys. Biol. 3, S10 (2006).

    CAS  PubMed  Google Scholar 

  25. 25.

    Gradišar, H. & Jerala, R. Self-assembled bionanostructures: proteins following the lead of DNA nanostructures. J. Nanobiotechnol. 12, 4 (2014).

    Google Scholar 

  26. 26.

    Desai, M. S. & Lee, S.-W. Protein-based functional nanomaterial design for bioengineering applications. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 7, 69–97 (2015).

    CAS  PubMed  Google Scholar 

  27. 27.

    Knowles, T. P. J. & Mezzenga, R. Amyloid fibrils as building blocks for natural and artificial functional materials. Adv. Mater. 28, 6546–6561 (2016).

    CAS  PubMed  Google Scholar 

  28. 28.

    Levin, A. et al. Ostwald’s rule of stages governs structural transitions and morphology of dipeptide supramolecular polymers. Nat. Commun. 5, 5219 (2014).

    CAS  PubMed  Google Scholar 

  29. 29.

    Gazit, E. Self-assembly of short aromatic peptides into amyloid fibrils and related nanostructures. Prion 1, 32–35 (2007).

    PubMed  PubMed Central  Google Scholar 

  30. 30.

    Levin, A. et al. Elastic instability-mediated actuation by a supra-molecular polymer. Nat. Phys. 12, 926–930 (2016).

    Google Scholar 

  31. 31.

    Maji, S. K. et al. Amyloid as a depot for the formulation of long-acting drugs. PLoS Biol. 6, e17 (2008).

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Standley, S. M. et al. Induction of cancer cell death by self-assembling nanostructures incorporating a cytotoxic peptide. Cancer Res. 70, 3020–3026 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Aggeli, A. et al. pH as a trigger of peptide β-sheet self-assembly and reversible switching between nematic and isotropic phases. J. Am. Chem. Soc. 125, 9619–9628 (2003).

    CAS  PubMed  Google Scholar 

  34. 34.

    Friggeri, A., Feringa, B. L. & van Esch, J. Entrapment and release of quinoline derivatives using a hydrogel of a low molecular weight gelator. J. Control. Release 97, 241–248 (2004).

    CAS  PubMed  Google Scholar 

  35. 35.

    Panda, J. J., Mishra, A., Basu, A. & Chauhan, V. S. Stimuli responsive self-assembled hydrogel of a low molecular weight free dipeptide with potential for tunable drug delivery. Biomacromolecules 9, 2244–2250 (2008).

    CAS  PubMed  Google Scholar 

  36. 36.

    Huang, R., Qi, W., Feng, L., Su, R. & He, Z. Self-assembling peptide–polysaccharide hybrid hydrogel as a potential carrier for drug delivery. Soft Matter 7, 6222–6230 (2011).

    CAS  Google Scholar 

  37. 37.

    Tjernberg, L. O. et al. Arrest of β-amyloid fibril formation by a pentapeptide ligand. J. Biol. Chem. 271, 8545–8548 (1996).

    CAS  PubMed  Google Scholar 

  38. 38.

    Krysmann, M. J., Castelletto, V. & Hamley, I. W. Fibrillisation of hydrophobically modified amyloid peptide fragments in an organic solvent. Soft Matter 3, 1401–1406 (2007).

    CAS  PubMed  Google Scholar 

  39. 39.

    Hamley, I. W. et al. Nematic and columnar ordering of a PEG–peptide conjugate in aqueous solution. Chem. Eur. J. 14, 11369–11375 (2008).

    CAS  PubMed  Google Scholar 

  40. 40.

    Castelletto, V., Cheng, G., Furzeland, S., Atkins, D. & Hamley, I. W. Control of strand registry by attachment of PEG chains to amyloid peptides influences nanostructure. Soft Matter 8, 5434–5438 (2012).

    CAS  Google Scholar 

  41. 41.

    Castelletto, V., Hamley, I. & Harris, P. J. F. Self-assembly in aqueous solution of a modified amyloid beta peptide fragment. Biophys. Chem. 138, 29–35 (2008).

    CAS  PubMed  Google Scholar 

  42. 42.

    Hauser, C. A. E. et al. Natural tri- to hexapeptides self-assemble in water to amyloid β-type fiber aggregates by unexpected α-helical intermediate structures. Proc. Natl Acad. Sci. USA 108, 1361–1366 (2011).

    CAS  PubMed  Google Scholar 

  43. 43.

    Lakshmanan, A. et al. Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis. Proc. Natl Acad. Sci. USA 110, 519–524 (2013).

    CAS  PubMed  Google Scholar 

  44. 44.

    Wang, J. et al. Trace water as prominent factor to induce peptide self-assembly: dynamic evolution and governing interactions in ionic liquids. Small 13, 1702175 (2017).

    Google Scholar 

  45. 45.

    Ren, X. et al. The dominant role of oxygen in modulating the chemical evolution pathways of tyrosine in peptides: dityrosine or melanin. Angew. Chem. Int. Ed. Engl. 58, 5872–5876 (2019).

    CAS  PubMed  Google Scholar 

  46. 46.

    Mason, T. O. et al. Expanding the solvent chemical space for self-assembly of dipeptide nanostructures. ACS Nano. 8, 1243–1253 (2014).

    CAS  PubMed  Google Scholar 

  47. 47.

    Yan, X. et al. Reversible transitions between peptide nanotubes and vesicle-like structures including theoretical modeling studies. Chem. Eur. J. 14, 5974–5980 (2008).

    CAS  PubMed  Google Scholar 

  48. 48.

    Yan, X. et al. Transition of cationic dipeptide nanotubes into vesicles and oligonucleotide delivery. Angew. Chem. Int. Ed. Engl. 46, 2431–2434 (2007).

    CAS  PubMed  Google Scholar 

  49. 49.

    Riley, J. M., Aggeli, A., Koopmans, R. J. & McPherson, M. J. Bioproduction and characterization of a pH responsive self-assembling peptide. Biotechnol. Bioeng. 103, 241–251 (2009).

    CAS  PubMed  Google Scholar 

  50. 50.

    Cinar, G. et al. Amyloid inspired self-assembled peptide nanofibers. Biomacromolecules 13, 3377–3387 (2012).

    CAS  PubMed  Google Scholar 

  51. 51.

    Du, Q. et al. A comparative study on the self-assembly of an amyloid-like peptide at water–solid interfaces and in bulk solutions. Microsc. Res. Tech. 78, 375–381 (2015).

    CAS  PubMed  Google Scholar 

  52. 52.

    Huettner, N., Dargaville, T. R. & Forget, A. Discovering cell-adhesion peptides in tissue engineering: beyond RGD. Trends Biotechnol. 36, 372–383 (2018).

    CAS  PubMed  Google Scholar 

  53. 53.

    Collier, J. H., Rudraa, J. S., Gasiorowskia, J. Z. & Jung, J. P. Multi-component extracellular matrices based on peptide self-assembly. Chem. Soc. Rev. 39, 3413–3424 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Liu, J. et al. Peptide glycosylation generates supramolecular assemblies from glycopeptides as biomimetic scaffolds for cell adhesion and proliferation. ACS Appl. Mater. Interfaces 8, 6917–6924 (2016).

    CAS  PubMed  Google Scholar 

  55. 55.

    Kisiday, J. et al. Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: implications for cartilage tissue repair. Proc. Natl Acad. Sci. USA 99, 9996–10001 (2002).

    CAS  PubMed  Google Scholar 

  56. 56.

    Kocabey, S., Ceylan, H., Tekinay, A. B. & Guler, M. O. Glycosaminoglycan mimetic peptide nanofibers promote mineralization by osteogenic cells. Acta Biomater. 9, 9075–9085 (2013).

    CAS  PubMed  Google Scholar 

  57. 57.

    O’Leary, L. E., Fallas, J. A., Bakota, E. L., Kang, M. K. & Hartgerink, J. D. Multi-hierarchical self-assembly of a collagen mimetic peptide from triple helix to nanofiber and hydrogel. Nat. Chem. 3, 821–828 (2011).

    PubMed  Google Scholar 

  58. 58.

    Kumar, V. A. et al. A nanostructured synthetic collagen mimic for hemostasis. Biomacromolecules 15, 1484–1490 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Bongiovanni, M. N., Scanlon, D. B. & Gras, S. L. Functional fibrils derived from the peptide TTR1-cycloRGDfK that target cell adhesion and spreading. Biomaterials 32, 6099–6110 (2011).

    CAS  PubMed  Google Scholar 

  60. 60.

    Reynolds, N. P., Charnley, M., Mezzenga, R. & Hartley, P. G. Engineered lysozyme amyloid fibril networks support cellular growth and spreading. Biomacromolecules 15, 599–608 (2014).

    CAS  PubMed  Google Scholar 

  61. 61.

    Kumar, V. A. et al. Self-assembling multidomain peptides tailor biological responses through biphasic release. Biomaterials 52, 71–78 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Das, S. et al. Implantable amyloid hydrogels for promoting stem cell differentiation to neurons. NPG Asia Mater. 8, e304 (2016).

    CAS  Google Scholar 

  63. 63.

    Jacob, R. S. et al. Self healing hydrogels composed of amyloid nano fibrils for cell culture and stem cell differentiation. Biomaterials 54, 97–105 (2015).

    CAS  PubMed  Google Scholar 

  64. 64.

    Kushwaha, M. et al. A nitric oxide releasing, self assembled peptide amphiphile matrix that mimics native endothelium for coating implantable cardiovascular devices. Biomaterials 31, 1502–1508 (2010).

    CAS  PubMed  Google Scholar 

  65. 65.

    Uzunalli, G. et al. Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels. Acta Biomater. 22, 8–18 (2015).

    CAS  PubMed  Google Scholar 

  66. 66.

    Berns, E. J. et al. A tenascin-C mimetic peptide amphiphile nanofiber gel promotes neurite outgrowth and cell migration of neurosphere-derived cells. Acta Biomater. 37, 50–58 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Freeman, R. et al. Reversible self-assembly of superstructured networks. Science 362, 808–813 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Panda, J. J., Dua, R., Mishra, A., Mittra, B. & Chauhan, V. S. 3D cell growth and proliferation on a RGD functionalized nanofibrillar hydrogel based on a conformationally restricted residue containing dipeptide. ACS Appl. Mater. Interfaces 2, 2839–2848 (2010).

    CAS  PubMed  Google Scholar 

  69. 69.

    Azevedo, H. S. & Pashkuleva, I. Biomimetic supramolecular designs for the controlled release of growth factors in bone regeneration. Adv. Drug Deliv. Rev. 94, 63–76 (2015).

    CAS  PubMed  Google Scholar 

  70. 70.

    Loo, Y. et al. Peptide bioink self-assembling nanofibrous scaffolds for three-dimensional organotypic cultures. Nano Lett. 15, 6919–6925 (2015).

    CAS  PubMed  Google Scholar 

  71. 71.

    Jacob, R. S. et al. Cell adhesion on amyloid fibrils lacking integrin recognition motif. J. Biol. Chem. 291, 5278–5298 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Vegas, A. J. et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat. Biotechnol. 34, 345–352 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Yesilyurt, V. et al. Injectable self-healing glucose-responsive hydrogels with pH-regulated mechanical properties. Adv. Mater. 28, 86–91 (2016).

    CAS  PubMed  Google Scholar 

  74. 74.

    Neal, R. A. et al. Three-dimensional elastomeric scaffolds designed with cardiac-mimetic structural and mechanical features. Tissue Eng. Part. A 19, 793–807 (2013).

    CAS  PubMed  Google Scholar 

  75. 75.

    Smith, D. J. et al. A multiphase transitioning peptide hydrogel for suturing ultrasmall vessels. Nat. Nanotechnol. 11, 95–102 (2016).

    CAS  PubMed  Google Scholar 

  76. 76.

    Dexter, A. F. & Middelberg, A. P. J. Peptides as functional surfactants. Ind. Eng. Chem. Res. 47, 6391–6398 (2008).

    CAS  Google Scholar 

  77. 77.

    Vauthey, S., Santoso, S., Gong, H., Watson, N. & Zhang, S. Molecular self-assembly of surfactant-like peptides to form nanotubes and nanovesicles. Proc. Natl Acad. Sci. USA 99, 5355–5360 (2002).

    CAS  PubMed  Google Scholar 

  78. 78.

    Braide-Moncoeur, O., Tran, N. T. & Long, J. R. Peptide-based synthetic pulmonary surfactant for the treatment of respiratory distress disorders. Curr. Opin. Chem. Biol. 32, 22–28 (2016).

    CAS  PubMed  Google Scholar 

  79. 79.

    Mondal, S. et al. A minimal length rigid helical peptide motif allows rational design of modular surfactants. Nat. Commun. 8, 14018 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Macindoe, I. et al. Self-assembly of functional, amphipathic amyloid monolayers by the fungal hydrophobin EAS. Proc. Natl Acad. Sci. USA 109, 804–811 (2012).

    Google Scholar 

  81. 81.

    Hanski, S. et al. Hierarchical ionic self-assembly of rod–comb block copolypeptide–surfactant complexes. Biomacromolecules 7, 3379–3384 (2006).

    CAS  PubMed  Google Scholar 

  82. 82.

    Zheng, X. et al. Expression, stabilization and purification of membrane proteins via diverse protein synthesis systems and detergents involving cell-free associated with self-assembly peptide surfactants. Biotechnol. Adv. 32, 564–574 (2014).

    CAS  PubMed  Google Scholar 

  83. 83.

    Chécot, F., Lecommandoux, S., Klok, H.-A. & Gnanou, Y. From supramolecular polymersomes to stimuli-responsive nano-capsules based on poly(diene-b-peptide) diblock copolymers. Eur. Phys. J. E 10, 25–35 (2003).

    PubMed  Google Scholar 

  84. 84.

    Bellomo, E. G., Wyrsta, M. D., Pakstis, L., Pochan, D. J. & Deming, T. J. Stimuli-responsive polypeptide vesicles by conformation-specific assembly. Nat. Mater. 3, 244–248 (2004).

    CAS  PubMed  Google Scholar 

  85. 85.

    Chen, C. et al. Molecular mechanisms of antibacterial and antitumor actions of designed surfactant-like peptides. Biomaterials 33, 592–603 (2012).

    CAS  PubMed  Google Scholar 

  86. 86.

    Delbecq, F. Supramolecular gels from lipopeptide gelators: template improvement and strategies for the in-situ preparation of inorganic nanomaterials and for the dispersion of carbon nanomaterials. Adv. Colloid Interface Sci. 209, 98–108 (2014).

    CAS  PubMed  Google Scholar 

  87. 87.

    Zhao, X. Design of self-assembling surfactant-like peptides and their applications. Curr. Opin. Colloid Interface Sci. 14, 340–348 (2009).

    CAS  Google Scholar 

  88. 88.

    Nagai, A., Nagai, Y., Qu, H. J. & Zhang, S. G. Dynamic behaviors of lipid-like self-assembling peptide A6D and A6K nanotubes. J. Nanosci. Nanotechnol. 7, 2246–2252 (2007).

    CAS  PubMed  Google Scholar 

  89. 89.

    Dehsorkhi, A., Castelletto, V. & Hamley, I. W. Self-assembling amphiphilic peptides. J. Pept. Sci. 20, 453–467 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Fatouros, D. G. et al. Lipid-like self-assembling peptide nanovesicles for drug delivery. ACS Appl. Mater. Interfaces 6, 8184–8189 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. 91.

    Pellach, M. et al. Spontaneous structural transition in phospholipid-inspired aromatic phosphopeptide nanostructures. ACS Nano 9, 4085–4095 (2015).

    CAS  PubMed  Google Scholar 

  92. 92.

    Pellach, M. et al. A two-tailed phosphopeptide crystallises to form a lamellar structure. Angew. Chem. Int. Ed. Engl. 56, 3252–3255 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Cheng, H. et al. Stem cell membrane engineering for cell rolling using peptide conjugation and tuning of cell-selectin interaction kinetics. Biomaterials 33, 5004–5012 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94.

    Lazzaro, B. P., Zasloff, M. & Rolff, J. Antimicrobial peptides: application informed by evolution. Science 368, eaau5480 (2020).

    CAS  PubMed  Google Scholar 

  95. 95.

    Jenssen, H., Hamill, P. & Hancock, R. E. W. Peptide antimicrobial agents. Clin. Microbiol. Rev. 19, 491–511 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. 96.

    Giuliani, A., Pirri, G. & Nicoletto, S. F. Antimicrobial peptides: an overview of a promising class of therapeutics. Cent. Eur. J. Biol. 2, 1–33 (2007).

    CAS  Google Scholar 

  97. 97.

    Seo, M.-D., Won, H.-S., Kim, J.-H., Mishig-Ochir, T. & Lee, B.-J. Antimicrobial peptides for therapeutic applications: a review. Molecules 17, 12276–12286 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. 98.

    Cederlund, A., Gudmundsson, G. H. & Agerberth, B. Antimicrobial peptides important in innate immunity. FEBS J. 278, 3942–3951 (2011).

    CAS  PubMed  Google Scholar 

  99. 99.

    Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 415, 389–395 (2002).

    CAS  PubMed  Google Scholar 

  100. 100.

    Timofeeva, L. & Kleshcheva, N. Antimicrobial polymers: mechanism of action, factors of activity, and applications. Appl. Microbiol. Biotechnol. 89, 475–492 (2011).

    CAS  PubMed  Google Scholar 

  101. 101.

    Nguyen, L. T., Haney, E. F. & Vogel, H. J. The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol. 29, 464–472 (2011).

    CAS  PubMed  Google Scholar 

  102. 102.

    Bahar, A. A. & Ren, D. Antimicrobial peptides. Pharmaceuticals 6, 1543–1575 (2013).

    PubMed  PubMed Central  Google Scholar 

  103. 103.

    Cudic, M. & Otvos, L. Intracellular targets of antibacterial peptides. Curr. Drug Targets 3, 101–106 (2002).

    CAS  PubMed  Google Scholar 

  104. 104.

    Brogden, K. A. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 3, 238–250 (2005).

    CAS  PubMed  Google Scholar 

  105. 105.

    Tew, G. N., Scott, R. W., Klein, M. L. & DeGrado, W. F. De novo design of antimicrobial polymers, foldamers, and small molecules: from discovery to practical applications. Acc. Chem. Res. 43, 30–39 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. 106.

    Giuliani, A. & Rinaldi, A. C. Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches. Cell. Mol. Life Sci. 68, 2255–2266 (2011).

    CAS  PubMed  Google Scholar 

  107. 107.

    Godballe, T., Nilsson, L. L., Petersen, P. D. & Jenssen, H. Antimicrobial β-peptides and α-peptoids. Chem. Biol. Drug Des. 77, 107–116 (2011).

    CAS  PubMed  Google Scholar 

  108. 108.

    Fjell, C. D., Hiss, J. A., Hancock, R. E. W. & Schneider, G. Designing antimicrobial peptides: form follows function. Nat. Rev. Drug Discov. 11, 37–51 (2012).

    CAS  Google Scholar 

  109. 109.

    McCloskey, A., Gilmore, B. & Laverty, G. Evolution of antimicrobial peptides to self-assembled peptides for biomaterial applications. Pathogens 3, 791–821 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. 110.

    Tian, X., Sun, F., Zhou, X. R., Luo, S. Z. & Chen, L. Role of peptide self-assembly in antimicrobial peptides. J. Pept. Sci. 21, 530–539 (2015).

    CAS  PubMed  Google Scholar 

  111. 111.

    Sun, L., Zheng, C. & Webster, T. J. Self-assembled peptide nanomaterials for biomedical applications: promises and pitfalls. Int. J. Nanomed. 12, 73–86 (2017).

    CAS  Google Scholar 

  112. 112.

    Salick, D. A., Pochan, D. J. & Schneider, J. P. Design of an injectable β-hairpin peptide hydrogel that kills methicillin-resistant Staphylococcus aureus. Adv. Mater. 21, 4120–4123 (2009).

    CAS  Google Scholar 

  113. 113.

    Rajagopal, K., Ozbas, B., Pochan, D. J. & Schneider, J. P. Probing the importance of lateral hydrophobic association in self-assembling peptide hydrogelators. Eur. Biophys. J. 35, 162–169 (2006).

    CAS  PubMed  Google Scholar 

  114. 114.

    Gupta, K. et al. Mechanism of membrane permeation induced by synthetic β-hairpin peptides. Biophys. J. 105, 2093–2103 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. 115.

    Kretsinger, J. K., Haines, L. A., Ozbas, B., Pochan, D. J. & Schneider, J. P. Cytocompatibility of self-assembled β-hairpin peptide hydrogel surfaces. Biomaterials 26, 5177–5186 (2005).

    CAS  PubMed  Google Scholar 

  116. 116.

    Haines, L. A. et al. Light-activated hydrogel formation via the triggered folding and self-assembly of a designed peptide. J. Am. Chem. Soc. 127, 17025–17029 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. 117.

    Haines-Butterick, L. et al. Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells. Proc. Natl Acad. Sci. USA 104, 7791–7796 (2007).

    CAS  PubMed  Google Scholar 

  118. 118.

    Veiga, A. S. et al. Arginine-rich self-assembling peptides as potent antibacterial gels. Biomaterials 33, 8907–8916 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. 119.

    Tripathi, J. K. et al. Variants of self-assembling peptide, KLD-12 that show both rapid fracture healing and antimicrobial properties. Biomaterials 56, 92–103 (2015).

    CAS  PubMed  Google Scholar 

  120. 120.

    Laverty, G. et al. Ultrashort cationic naphthalene-derived self-assembled peptides as antimicrobial nanomaterials. Biomacromolecules 15, 3429–3439 (2014).

    CAS  PubMed  Google Scholar 

  121. 121.

    McCloskey, A. P., Draper, E. R., Gilmore, B. F. & Laverty, G. Ultrashort self-assembling Fmoc-peptide gelators for anti-infective biomaterial applications. J. Pept. Sci. 23, 131–140 (2017).

    CAS  PubMed  Google Scholar 

  122. 122.

    Gahane, A. Y. et al. Fmoc-phenylalanine displays antibacterial activity against Gram-positive bacteria in gel and solution phases. Soft Matter 14, 2234–2244 (2018).

    CAS  PubMed  Google Scholar 

  123. 123.

    Hughes, M., Debnath, S., Knapp, C. W. & Ulijn, R. V. Antimicrobial properties of enzymatically triggered self-assembling aromatic peptide amphiphiles. Biomater. Sci. 1, 1138–1142 (2013).

    CAS  PubMed  Google Scholar 

  124. 124.

    Yang, Z., Liang, G., Guo, Z., Guo, Z. & Xu, B. Intracellular hydrogelation of small molecules inhibits bacterial growth. Angew. Chem. Int. Ed. Engl. 46, 8216–8219 (2007).

    CAS  PubMed  Google Scholar 

  125. 125.

    Marchesan, S. et al. Self-assembly of ciprofloxacin and a tripeptide into an antimicrobial nanostructured hydrogel. Biomaterials 34, 3678–3687 (2013).

    CAS  PubMed  Google Scholar 

  126. 126.

    Hu, Y. et al. Self-assembled peptide nanofibers encapsulated with superfine silver nanoparticles via Ag+ coordination. Langmuir 31, 8599–8605 (2015).

    CAS  PubMed  Google Scholar 

  127. 127.

    Paladini, F. et al. Silver-doped self-assembling di-phenylalanine hydrogels as wound dressing biomaterials. J. Mater. Sci. Mater. Med. 24, 2461–2472 (2013).

    CAS  PubMed  Google Scholar 

  128. 128.

    Jiang, L., Xu, D., Sellati, T. J. & Dong, H. Self-assembly of cationic multidomain peptide hydrogels: supramolecular nanostructure and rheological properties dictate antimicrobial activity. Nanoscale 7, 19160–19169 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. 129.

    Liu, Y., Yang, Y., Wang, C. & Zhao, X. Stimuli-responsive self-assembling peptides made from antibacterial peptides. Nanoscale 5, 6413–6421 (2013).

    CAS  PubMed  Google Scholar 

  130. 130.

    Fernandez-Lopez, S. et al. Antibacterial agents based on the cyclic d,l-α-peptide architecture. Nature 412, 452–455 (2001).

    CAS  PubMed  Google Scholar 

  131. 131.

    Horne, W. S. et al. Antiviral cyclic d,l-α-peptides: targeting a general biochemical pathway in virus infections. Bioorg. Med. Chem. 13, 5145–5153 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. 132.

    Montero, A. et al. Self-assembling peptide nanotubes with antiviral activity against hepatitis C virus. Chem. Biol. 18, 1453–1462 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. 133.

    Bionda, N. et al. Effects of cyclic lipodepsipeptide structural modulation on stability, antibacterial activity, and human cell toxicity. ChemMedChem 7, 871–882 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. 134.

    Fletcher, J. T., Finlay, J. A., Callow, M. E., Callow, J. A. & Ghadiri, M. R. A combinatorial approach to the discovery of biocidal six-residue cyclic d,l-α-peptides against bacteria methicillin-resistant Staphylococcus aureus (MRSA) and E. coli and the biofouling algae Ulva linza and Navicula perminuta. Chemistry 13, 4008–4013 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. 135.

    Bionda, N. et al. Identification of novel cyclic lipopeptides from a positional scanning combinatorial library with enhanced antibacterial and antibiofilm activities. Eur. J. Med. Chem. 108, 354–363 (2016).

    CAS  PubMed  Google Scholar 

  136. 136.

    Liu, L. et al. Self-assembled cationic peptide nanoparticles as an efficient antimicrobial agent. Nat. Nanotechnol. 4, 457–463 (2009).

    CAS  PubMed  Google Scholar 

  137. 137.

    Xu, K. et al. Efficacy of CG3R6TAT nanoparticles self-assembled from a novel antimicrobial peptide for the treatment of Candida albicans meningitis in rabbits. Chemotherapy 57, 417–425 (2012).

    Google Scholar 

  138. 138.

    Makovitzki, A., Baram, J. & Shai, Y. Antimicrobial lipopolypeptides composed of palmitoyl di- and tricationic peptides: In vitro and in vivo activities, self-assembly to nanostructures, and a plausible mode of action. Biochemistry 47, 10630–10636 (2008).

    CAS  PubMed  Google Scholar 

  139. 139.

    Chen, C. et al. Antibacterial activities of short designer peptides: A link between propensity for nanostructuring and capacity for membrane destabilization. Biomacromolecules 11, 402–411 (2010).

    CAS  PubMed  Google Scholar 

  140. 140.

    Beter, M. et al. Multivalent presentation of cationic peptides on supramolecular nanofibers for antimicrobial activity. Mol. Pharm. 4, 3660–3668 (2017).

    Google Scholar 

  141. 141.

    Schnaider, L. et al. Self-assembling dipeptide antibacterial nanostructures with membrane disrupting activity. Nat. Commun. 8, 1365 (2017).

    PubMed  PubMed Central  Google Scholar 

  142. 142.

    Salinas, N., Colletier, J. P., Moshe, A. & Landau, M. Extreme amyloid polymorphism in Staphylococcus aureus virulent PSMα peptides. Nat. Commun. 9, 3512 (2018).

    PubMed  PubMed Central  Google Scholar 

  143. 143.

    Deslouches, B. & Di, Y. P. Antimicrobial peptides with selective antitumor mechanisms: Prospect for anticancer applications. Oncotarget 8, 46635–46651 (2017).

    PubMed  PubMed Central  Google Scholar 

  144. 144.

    Felício, M. R., Silva, O. N., Gonçalves, S., Santos, N. C. & Franco, O. L. Peptides with dual antimicrobial and anticancer activities. Front. Chem. 5, 5 (2017).

    PubMed  PubMed Central  Google Scholar 

  145. 145.

    Gaspar, D., Veiga, A. S. & Castanho, M. A. R. B. From antimicrobial to anticancer peptides. A review. Front. Microbiol. 4, 294 (2013).

    PubMed  PubMed Central  Google Scholar 

  146. 146.

    Ding, Y. et al. Improvement of stability and efficacy of C16Y therapeutic peptide via molecular self-assembly into tumor-responsive nanoformulation. Mol. Cancer Ther. 14, 2390–2400 (2015).

    CAS  PubMed  Google Scholar 

  147. 147.

    Ding, Y. et al. Targeting vault nanoparticles to specific cell surface receptors. ACS Nano 3, 27–36 (2009).

    Google Scholar 

  148. 148.

    Tang, A., Wang, C., Stewart, R. & Kopecek, J. Self-assembled peptides exposing epitopes recognizable by human lymphoma cells. Bioconjug. Chem. 11, 363–371 (2000).

    CAS  PubMed  Google Scholar 

  149. 149.

    Zha, R. H. et al. Supramolecular assembly of multifunctional maspin-mimetic nanostructures as a potent peptide-based angiogenesis inhibitor. Acta Biomater. 12, 1–10 (2015).

    PubMed  Google Scholar 

  150. 150.

    Levin, A. et al. Self-assembly-mediated release of peptide nanoparticles through jets across microdroplet interfaces. ACS Appl. Mater. Interfaces 10, 27578–27583 (2018).

    CAS  PubMed  Google Scholar 

  151. 151.

    Ding, Y. et al. Gene delivery and immunomodulatory effects of plasmid DNA associated with branched amphiphilic peptide capsules. J. Control. Release 241, 15–24 (2016).

    Google Scholar 

  152. 152.

    Mumcuoglu, D. et al. Cellular internalization of therapeutic oligonucleotides by peptide amphiphile nanofibers and nanospheres. ACS Appl. Mater. Interfaces 8, 11280–11287 (2016).

    CAS  PubMed  Google Scholar 

  153. 153.

    Li, Y. et al. Self-assembled peptide (CADY-1) improved the clinical application of doxorubicin. Int. J. Pharm. 434, 209–214 (2012).

    CAS  PubMed  Google Scholar 

  154. 154.

    Sarangthem, V. et al. Multivalent targeting based delivery of therapeutic peptide using AP1-ELP carrier for effective cancer therapy. Theranostics 6, 2235–2249 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. 155.

    Zha, R. H., Sur, S. & Stupp, S. I. Self-assembly of cytotoxic peptide amphiphiles into supramolecular membranes for cancer therapy. Adv. Healthc. Mater. 2, 126–133 (2013).

    CAS  PubMed  Google Scholar 

  156. 156.

    Qiao, Z. Y. et al. Self-assembled ROS-sensitive polymer-peptide therapeutics incorporating built-in reporters for evaluation of treatment efficacy. Biomacromolecules 17, 1643–1652 (2016).

    CAS  PubMed  Google Scholar 

  157. 157.

    Chen, L., Patrone, N. & Liang, J. F. Peptide self-assembly on cell membranes to induce cell lysis. Biomacromolecules 13, 3327–3333 (2012).

    CAS  PubMed  Google Scholar 

  158. 158.

    Ding, Y. et al. Smac therapeutic peptide nanoparticles inducing apoptosis of cancer cells for combination chemotherapy with doxorubicin. ACS Appl. Mater. Interfaces 7, 8005–8012 (2015).

    Google Scholar 

  159. 159.

    Chen, J. et al. Transmembrane delivery of anticancer drugs through self-assembly of cyclic peptide nanotubes. Nanoscale 8, 7127–7136 (2016).

    CAS  PubMed  Google Scholar 

  160. 160.

    Soukasene, S. et al. Antitumor activity of peptide amphiphile nanofiber-encapsulated camptothecin. ACS Nano 5, 9113–9121 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  161. 161.

    Liu, K. et al. Simple peptide-tuned self-assembly of photosensitizers towards anticancer photodynamic therapy. Angew. Chem. Int. Ed. Engl. 55, 3036–3039 (2016).

    CAS  PubMed  Google Scholar 

  162. 162.

    Zou, Q. et al. Biological photothermal nanodots based on self-assembly of peptide-porphyrin conjugates for antitumor therapy. J. Am. Chem. Soc. 139, 1921–1927 (2017).

    CAS  PubMed  Google Scholar 

  163. 163.

    Xing, R. et al. Self-assembling endogenous biliverdin as a versatile near-infrared photothermal nanoagent for cancer theranostics. Adv. Mater. 31, 1900822 (2019).

    Google Scholar 

  164. 164.

    Fan, Z., Sun, L., Huang, Y., Wang, Y. & Zhang, M. Bioinspired fluorescent dipeptide nanoparticles for targeted cancer cell imaging and real-time monitoring of drug release. Nat. Nanotechnol. 11, 388–394 (2016).

    CAS  PubMed  Google Scholar 

  165. 165.

    Hyman, A. A., Weber, C. A. & Jülicher, F. Liquid–liquid phase separation in biology. Annu. Rev. Cell Dev. Biol. 30, 39–58 (2014).

    CAS  PubMed  Google Scholar 

  166. 166.

    Banani, S. F., Lee, H. O., Hyman, A. A. & Rosen, M. K. Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell. Biol. 18, 285–298 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. 167.

    Shin, Y. & Brangwynne, C. P. Liquid phase condensation in cell physiology and disease. Science 357, eaaf4382 (2017).

    PubMed  Google Scholar 

  168. 168.

    Qamar, S. et al. FUS phase separation is modulated by a molecular chaperone and methylation of arginine cation-π interactions. Cell 173, 720–734 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  169. 169.

    Alberti, S. & Dormann, D. Liquid–liquid phase separation in disease. Annu. Rev. Genet. 53, 171–194 (2019).

    CAS  PubMed  Google Scholar 

  170. 170.

    Boeynaems, S. et al. Protein phase separation: a new phase in cell biology. Trends Cell Biol. 28, 420–435 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. 171.

    Lee, K.-H. et al. C9orf72 dipeptide repeats impair the assembly, dynamics, and function of membrane-less organelles. Cell 167, 774–788 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  172. 172.

    Nakashima, K. K., Vibhute, M. A. & Spruijt, E. Biomolecular chemistry in liquid phase separated compartments. Front. Mol. Biosci. 6, 21 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. 173.

    Bentley, E. P., Frey, B. B. & Deniz, A. A. Physical chemistry of cellular liquid-phase separation. Chem. Eur. J. 25, 5600–5610 (2019).

    CAS  PubMed  Google Scholar 

  174. 174.

    Wang, J. et al. A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins. Cell 174, 688–699 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. 175.

    Onuchic, P. L., Milin, A. N., Alshareedah, I., Deniz, A. A. & Banerjee, P. R. Divalent cations can control a switch-like behavior in heterotypic and homotypic RNA coacervates. Sci. Rep. 9, 12161 (2019).

    PubMed  PubMed Central  Google Scholar 

  176. 176.

    Sanders, D. W. et al. Competing protein–RNA interaction networks control multiphase intracellular organization. Cell 181, 306–324 (2020).

    CAS  PubMed  Google Scholar 

  177. 177.

    Alberti, S., Gladfelter, A. & Mittag, T. Considerations and challenges in studying liquid–liquid phase separation and biomolecular condensates. Cell 176, 419–434 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  178. 178.

    Shin, Y. et al. Spatiotemporal control of intracellular phase transitions using light-activated optoDroplets. Cell 168, 159–171 (2017).

    CAS  PubMed  Google Scholar 

  179. 179.

    Schuster, B. S. et al. Controllable protein phase separation and modular recruitment to form responsive membraneless organelles. Nat. Commun. 9, 2985 (2018).

    PubMed  PubMed Central  Google Scholar 

  180. 180.

    Linsenmeier, M. et al. Dynamics of synthetic membraneless organelles in microfluidic droplets. Angew. Chem. Int. Ed. Engl. 58, 14489–14494 (2019).

    CAS  PubMed  Google Scholar 

  181. 181.

    Quiroz, F. G. & Chilkoti, A. Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers. Nat. Mater. 14, 1164–1171 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. 182.

    Simon, J. R., Carroll, N. J., Rubinstein, M., Chilkoti, A. & López, G. P. Programming molecular self-assembly of intrinsically disordered proteins containing sequences of low complexity. Nat. Chem. 9, 509–515 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  183. 183.

    Reinkemeier, C. D., Girona, G. E. & Lemke, E. A. Designer membraneless organelles enable codon reassignment of selected mRNAs in eukaryotes. Science 363, eaaw2644 (2019).

    CAS  PubMed  Google Scholar 

  184. 184.

    Uversky, V. N. Natively unfolded proteins: a point where biology waits for physics. Protein Sci. 11, 739–756 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  185. 185.

    Martin, E. W. & Mittag, T. Relationship of sequence and phase separation in protein low-complexity regions. Biochemistry 57, 2478–2487 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. 186.

    Hughes, M. P. et al. Atomic structures of low-complexity protein segments reveal kinked β sheets that assemble networks. Science 359, 698–701 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  187. 187.

    Kato, M. et al. Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels. Cell 149, 753–767 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  188. 188.

    Xiang, S. et al. The LC domain of hnRNPA2 adopts similar conformations in hydrogel polymers, liquid-like droplets, and nuclei. Cell 5, 829–839 (2015).

    Google Scholar 

  189. 189.

    Renton, A. E. et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, 257–268 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  190. 190.

    Wang, Y., Lomakin, A., Kanai, S., Alex, R. & Benedek, G. B. Liquid–liquid phase separation in oligomeric peptide solutions. Langmuir 33, 7715–7721 (2017).

    CAS  PubMed  Google Scholar 

  191. 191.

    Ulijn, R. V. & Lampel, A. Order/disorder in protein and peptide-based biomaterials. Isr. J. Chem. 59, 1–13 (2019).

    Google Scholar 

  192. 192.

    Lee, K. H. et al. C9orf72 dipeptide repeats impair the assembly, dynamics, and function of membrane-less organelles. Cell 167, 774–788 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  193. 193.

    Lin, Y. et al. Toxic PR poly-dipeptides encoded by the C9orf72 repeat expansion target LC domain polymers. Cell 167, 789–802 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  194. 194.

    Boeynaems, S. et al. Phase separation of C9orf72 dipeptide repeats perturbs stress granule dynamics. Mol. Cell 65, 1044–1055 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  195. 195.

    Aumiller, W. M. Jr RNA-based coacervates as a model for membraneless organelles: formation, properties, and interfacial liposome assembly. Langmuir 32, 10042–10053 (2016).

    CAS  PubMed  Google Scholar 

  196. 196.

    Aumiller, W. M. Jr & Keating, C. D. Phosphorylation-mediated RNA/peptide complex coacervation as a model for intracellular liquid organelles. Nat. Chem. 8, 129–137 (2016).

    CAS  PubMed  Google Scholar 

  197. 197.

    Lu, T. & Spruijt, E. Multiphase complex coacervate droplets. J. Am. Chem. Soc. 142, 2905–2914 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  198. 198.

    Vieregg, J. R. et al. Oligonucleotide–peptide complexes: phase control by hybridization. J. Am. Chem. Soc. 140, 1632–1638 (2018).

    CAS  PubMed  Google Scholar 

  199. 199.

    Cao, M. et al. Peptide-induced DNA condensation into virus-mimicking nanostructures. ACS Appl. Mater. Interfaces 10, 24349–24360 (2018).

    CAS  PubMed  Google Scholar 

  200. 200.

    Yuan, C. et al. Nucleation and growth of amino-acid and peptide supramolecular polymers through liquid–liquid phase separation. Angew. Chem. Int. Ed. Engl. 58, 18116–18123 (2019).

    CAS  PubMed  Google Scholar 

  201. 201.

    Reznikov, N., Steele, J. A. M., Fratzl, P. & Stevens, M. M. A materials science vision of extracellular matrix mineralization. Nat. Rev. Mater. 1, 16041 (2016).

    CAS  Google Scholar 

  202. 202.

    Espinosa, A. D., Rim, J. E., Barthelat, F. & Buehler, B. J. Merger of structure and material in nacre and bone — perspectives on de novo biomimetic materials. Prog. Mater. Sci. 54, 1059–1100 (2009).

    CAS  Google Scholar 

  203. 203.

    Chiti, F. & Dobson, C. M. Protein misfolding, amyloid formation, and human disease: A summary of progress over the last decade. Annu. Rev. Biochem. 86, 27–68 (2017).

    CAS  PubMed  Google Scholar 

  204. 204.

    Cao, Y., Bolisetty, S., Wolfisberg, G., Adamcik, J. & Mezzenga, R. Amyloid fibril-directed synthesis of silica core–shell nanofilaments, gels, and aerogels. Proc. Natl Acad. Sci. USA 116, 4012–4017 (2019).

    CAS  PubMed  Google Scholar 

  205. 205.

    Li, C. et al. Amyloid-hydroxyapatite bone biomimetic composites. Adv. Mater. 26, 3207–3212 (2014).

    CAS  PubMed  Google Scholar 

  206. 206.

    Le Norcy, E. et al. Phosphorylated and non-phosphorylated leucine rich amelogenin peptide differentially affect ameloblast mineralization. Front. Physiol. 9, 55 (2018).

    PubMed  PubMed Central  Google Scholar 

  207. 207.

    Tavafoghi, M. & Cerruti, M. The role of amino acids in hydroxyapatite mineralization. J. R. Soc. Interface 13, 20160462 (2016).

    PubMed  PubMed Central  Google Scholar 

  208. 208.

    Newcomb, C. J., Bitton, R., Velichko, Y. S., Snead, M. L. & Stupp, S. I. The role of nanoscale architecture in supramolecular templating of biomimetic hydroxyapatite mineralization. Small 8, 2195–2202 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  209. 209.

    Lechner, C. C. & Becker, C. F. W. A sequence-function analysis of the silica precipitating silaffin R5 peptide. J. Pept. Sci. 20, 152–158 (2014).

    CAS  PubMed  Google Scholar 

  210. 210.

    Diaz, D., Care, A. & Sunna, A. Bioengineering strategies for protein-based nanoparticles. Genes 9, 370 (2018).

    PubMed Central  Google Scholar 

  211. 211.

    Oh, D. et al. M13 virus-directed synthesis of nanostructured metal oxides for lithium–oxygen batteries. Nano Lett. 14, 4837–4845 (2014).

    CAS  PubMed  Google Scholar 

  212. 212.

    Courchesne, N.-M. D. et al. Constructing multifunctional virus-templated nanoporous composites for thin film solar cells: contributions of morphology and optics to photocurrent generation. J. Phys. Chem. C 119, 13987–14000 (2015).

    Google Scholar 

  213. 213.

    Nyström, G., Fernández-Ronco, M. P., Bolisetty, S., Mazzotti, M. & Mezzenga, R. Amyloid templated gold aerogels. Adv. Mater. 28, 472–478 (2016).

    PubMed  Google Scholar 

  214. 214.

    Bolisetty, S. & Mezzenga, R. Amyloid–carbon hybrid membranes for universal water purification. Nat. Nanotechnol. 11, 365–371 (2016).

    CAS  PubMed  Google Scholar 

  215. 215.

    Ding, Y. et al. Self-assembly of antimicrobial peptides on gold nanodots: against multidrug-resistant bacteria and wound-healing application. Adv. Funct. Mater. 25, 7189–7199 (2015).

    Google Scholar 

  216. 216.

    Ding, Y. et al. Silver mineralization on self-assembled peptide nanofibers for long term antimicrobial effect. J. Mater. Chem. 22, 2575–2581 (2012).

    Google Scholar 

  217. 217.

    Ji, W. et al. Metal-ion modulated structural transformation of amyloid-like dipeptide supramolecular self-assembly. ACS Nano 13, 7300–7309 (2019).

    CAS  PubMed  Google Scholar 

  218. 218.

    Yan, X., Zhu, P., Fei, J. & Li, J. Self-assembly of peptide-inorganic hybrid spheres for adaptive encapsulation of guests. Adv. Mater. 22, 1283–1287 (2010).

    CAS  PubMed  Google Scholar 

  219. 219.

    Hamely, I. A., Kirkham, S., Dehsorkhi, A. & Castelletto, V. Self-assembly of a model peptide incorporating a hexa-histidine sequence attached to an oligo-alanine sequence, and binding to gold NTA/nickel nanoparticles. Biomacromolecules 15, 3412–3420 (2014).

    Google Scholar 

  220. 220.

    Stevens, M. M., Flynn, N. T., Wang, C., Tirrell, D. A. & Langer, R. Coiled-coil peptide-based assembly of gold nanoparticles. Adv. Mater. 16, 915–918 (2004).

    CAS  Google Scholar 

  221. 221.

    Fichman, G. et al. Seamless metallic coating and surface adhesion of self-assembled bioinspired nanostructures based on di-(3,4-dihydroxy-l-phenylalanine) peptide motif. ACS Nano 8, 7220–7228 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  222. 222.

    Guterman, T. et al. Electrical conductivity, selective adhesion, and biocompatibility in bacteria-inspired peptide–metal self-supporting nanocomposites. Adv. Mater. 31, 1807285 (2019).

    Google Scholar 

  223. 223.

    Liu, Q., Wang, H., Shi, X., Wang, Z.-G. & Ding, B. Self-assembled DNA/peptide-based nanoparticle exhibiting synergistic enzymatic activity. ACS Nano 11, 7251–7258 (2017).

    CAS  PubMed  Google Scholar 

  224. 224.

    Liu, K. et al. Mimicking primitive photobacteria: sustainable hydrogen evolution based on peptide–porphyrin co-assemblies with a self-mineralized reaction center. Angew. Chem. Int. Ed. Engl. 55, 12503–12507 (2016).

    CAS  PubMed  Google Scholar 

  225. 225.

    Liu, K., Zhang, H., Xing, R., Zou, Q. & Yan, X. Biomimetic oxygen-evolving photobacteria based on amino acid and porphyrin hierarchical self-organization. ACS Nano 11, 12840–12848 (2017).

    CAS  PubMed  Google Scholar 

  226. 226.

    Han, J., Liu, K., Chang, R., Zhao, L. & Yan, X. Photooxidase-mimicking nanovesicles with superior photocatalytic activity and stability based on amphiphilic amino acid and phthalocyanine co-assembly. Angew. Chem. Int. Ed. Engl. 58, 2000–2004 (2019).

    CAS  PubMed  Google Scholar 

  227. 227.

    Jiang, L., Yang, S., Lund, R. & Dong, H. Shape-specific nanostructured protein mimics from de novo designed chimeric peptides. Biomater. Sci. 6, 272–279 (2018).

    CAS  PubMed  Google Scholar 

  228. 228.

    Nambiar, M., Wang, L.-S., Rotello, V. & Chmielewski, J. Reversible hierarchical assembly of trimeric coiled-coil peptides into banded nano- and microstructures. J. Am. Chem. Soc. 140, 13028–13033 (2018).

    CAS  PubMed  Google Scholar 

  229. 229.

    Yuan, C. et al. Hierarchically oriented organization in supramolecular peptide crystals. Nat. Rev. Chem. 3, 567–588 (2019).

    CAS  Google Scholar 

  230. 230.

    Ardoña, H. A. M. & Tovar, J. D. Peptide π electron conjugates: organic electronics for biology? Bioconjugate Chem. 26, 2290–2302 (2015).

    Google Scholar 

  231. 231.

    Panda, S. S., Katz, H. E. & Tovar, J. D. Solid-state electrical applications of protein and peptide based nanomaterials. Chem. Soc. Rev. 47, 3640–3658 (2018).

    CAS  PubMed  Google Scholar 

  232. 232.

    Tao, K., Makam, P., Aizen, R. & Gazit, E. Self-assembling peptide semiconductors. Science 358, eaam9756 (2017).

    PubMed  PubMed Central  Google Scholar 

  233. 233.

    Sun, B. et al. Photoactive properties of supramolecular assembled short peptides. Chem. Soc. Rev. 48, 4387–4400 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  234. 234.

    Gazit, E. Aromatic dipeptides light up. Nat. Nanotechnol. 11, 309–310 (2016).

    CAS  PubMed  Google Scholar 

  235. 235.

    Ni, N. et al. Self-assembling amyloid-like peptides as exogenous second harmonic probes for bioimaging applications. J. Biophotonics 12, e201900065 (2019).

    CAS  PubMed  Google Scholar 

  236. 236.

    Chen, Y. et al. High-efficiency fluorescence through bioinspired supramolecular self-assembly. ACS Nano 14, 2798–2807 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  237. 237.

    Lou, S., Wang, X., Yu, Z. & Shi, L. Peptide tectonics: encoded structural complementarity dictates programmable self-assembly. Adv. Sci. 6, 1802043 (2019).

    Google Scholar 

  238. 238.

    John, E. A., Massena, C. J. & Berryman, O. B. Helical anion foldamers in solution. Chem. Rev. 120, 2759–2782 (2020).

    CAS  PubMed  Google Scholar 

  239. 239.

    Yoo, S. H. & Lee, H.-S. Foldectures: 3D molecular architectures from self-assembly of peptide foldamers. Acc. Chem. Res. 50, 832–841 (2017).

    CAS  PubMed  Google Scholar 

  240. 240.

    Martinek, T. A. & Fülöp, F. Peptidic foldamers: ramping up diversity. Chem. Soc. Rev. 41, 687–702 (2012).

    CAS  PubMed  Google Scholar 

  241. 241.

    Valery, C. et al. Biomimetic organization: Octapeptide self-assembly into nanotubes of viral capsid-like dimension. Proc. Natl Acad. Sci. USA 100, 10258–10262 (2003).

    CAS  PubMed  Google Scholar 

  242. 242.

    Matsuura, K. Synthetic approaches to construct viral capsid-like spherical nanomaterials. Chem. Commun. 54, 8944–8959 (2018).

    CAS  Google Scholar 

  243. 243.

    Matsuura, K. & Honjo, T. Artificial viral capsid dressed up with human serum albumin. Bioconjugate Chem. 30, 1636–1641 (2019).

    CAS  Google Scholar 

  244. 244.

    Matsuura, K., Ota, J., Fujita, S., Shiomi, Y. & Inaba, H. Construction of ribonuclease-decorated artificial virus-like capsid by peptide self-assembly. J. Org. Chem. 85, 1668–1673 (2020).

    CAS  PubMed  Google Scholar 

  245. 245.

    Ni, R. & Chau, Y. Structural mimics of viruses through peptide/DNA co-assembly. J. Am. Chem. Soc. 136, 17902–17905 (2014).

    CAS  PubMed  Google Scholar 

  246. 246.

    Ni, R. & Chau, Y. Tuning the inter-nanofibril interaction to regulate the morphology and function of peptide/DNA co-assembled viral mimics. Angew. Chem. Int. Ed. Engl. 56, 9356–9360 (2017).

    CAS  PubMed  Google Scholar 

  247. 247.

    Ni, R. & Chau, Y. Nanoassembly of oligopeptides and DNA mimics the sequential disassembly of a spherical virus. Angew. Chem. Int. Ed. Engl. 59, 3578–3584 (2020).

    CAS  PubMed  Google Scholar 

  248. 248.

    Zhang, C. et al. Virus-inspired self-assembled nanofibers with aggregation-induced emission for highly efficient and visible gene delivery. ACS Appl. Mater. Interfaces 9, 4425–4432 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  249. 249.

    Parodi, A. et al. Bio-inspired engineering of cell- and virus-like nanoparticles for drug delivery. Biomaterials 147, 155–168 (2017).

    CAS  PubMed  Google Scholar 

  250. 250.

    Cai, Y. et al. Recent progress in supramolecular peptide assemblies as virus mimics for cancer immunotherapy. Biomater. Sci. 8, 1045–1057 (2020).

    CAS  PubMed  Google Scholar 

  251. 251.

    Knowles, T. P. J., Vendruscolo, M. & Dobson, C. M. The amyloid state and its association with protein misfolding diseases. Nat. Rev. Mol. Cell Biol. 15, 384–396 (2014).

    CAS  PubMed  Google Scholar 

  252. 252.

    Cohen, S. I. A., Vendruscolo, M., Dobson, C. M. & Knowles, T. P. J. Nucleated polymerization with secondary pathways. III. Equilibrium behavior and oligomer populations. J. Chem. Phys. 135, 065107 (2011).

    PubMed  PubMed Central  Google Scholar 

  253. 253.

    Knowles, T. P. J. et al. An analytical solution to the kinetics of breakable filament assembly. Science 326, 1533–1537 (2009).

    CAS  PubMed  Google Scholar 

  254. 254.

    Dobson, C. M. Chemical space and biology. Nature 432, 824–828 (2004).

    CAS  PubMed  Google Scholar 

  255. 255.

    Cohen, S. I. A. et al. Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism. Proc. Natl Acad. Sci. USA 110, 9758–9763 (2013).

    CAS  PubMed  Google Scholar 

  256. 256.

    Fowler, D. M., Koulov, A. T., Balch, W. E. & Kelly, J. W. Functional amyloid — from bacteria to humans. Trends Biochem. Sci. 32, 217–224 (2007).

    CAS  PubMed  Google Scholar 

  257. 257.

    Otzen, D. & Riek, R. Functional amyloids. Cold Spring Harb. Perspect. Biol. 11, a033860 (2019).

    CAS  PubMed  Google Scholar 

  258. 258.

    Appel, E. A. et al. Self-assembled hydrogels utilizing polymer–nanoparticle interactions. Nat. Commun. 6, 6295 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  259. 259.

    Benton, G., Arnaoutova, I., George, J., Kleinman, H. K. & Koblinski, J. Matrigel: from discovery and ECM mimicry to assays and models for cancer research. Adv. Drug Deliv. Rev. 79–80, 3–18 (2014).

    PubMed  Google Scholar 

  260. 260.

    Panda, J. J. & Chauhan, V. S. Short peptide based self-assembled nanostructures: implications in drug delivery and tissue engineering. Polym. Chem. 5, 4418–4436 (2014).

    Google Scholar 

  261. 261.

    Hamley, I. W. et al. Self-assembly of a model amphiphilic oligopeptide incorporating an arginine headgroup. Soft Matter 9, 4794–4801 (2013).

    CAS  Google Scholar 

  262. 262.

    Fleming, S., Debnath, S., Frederix, P. W., Hunt, N. T. & Ulijn, R. V. Insights into the coassembly of hydrogelators and surfactants based on aromatic peptide amphiphiles. Biomacromolecules 15, 1171–1184 (2014).

    CAS  PubMed  Google Scholar 

  263. 263.

    Liyanage, W., Vats, K., Rajbhandary, A., Benoit, D. S. & Nilsson, B. L. Multicomponent dipeptide hydrogels as extracellular matrix-mimetic scaffolds for cell culture applications. Chem. Commun. 51, 11260–11263 (2015).

    CAS  Google Scholar 

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Acknowledgements

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 675007 (T.A.H., G.J.L.B. and T.P.J.K.), the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) through the ERC grant PhysProt grant agreement 337969 (A.L. and T.P.J.K.) and the European Research Council under the European Union’s Horizon 2020 research and innovation programme BISON grant agreement 694426 (L.S. and E.G.). We also thank the Newman Foundation (T.P.J.K.), the Oppenheimer Early Career Fellowship (A.L.), the Israeli Ministry of Science, Technology and Space (L.S.), the BBSRC (T.P.J.K.), the Royal Society (URF\R\180019, G.J.L.B.), FCT Portugal (FCT Investigator IF/00624/2015 to G.J.L.B.), the Israeli National Nanotechnology Initiative and Helmsley Charitable Trust (E.G.), Elan Pharmaceuticals (T.P.J.K.) and the Centre for Misfolding Diseases (A.L. and T.P.J.K.) for financial support. We are grateful to our late colleague and friend Chris Dobson for input into this Review.

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A.L., T.A.H and L.S. contributed equally to this work. A.L., G.J.L.B., E.G. and T.P.J.K. conceived the Review. All authors contributed to the discussion and writing of the Review.

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Correspondence to Tuomas P. J. Knowles.

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Levin, A., Hakala, T.A., Schnaider, L. et al. Biomimetic peptide self-assembly for functional materials. Nat Rev Chem (2020). https://doi.org/10.1038/s41570-020-0215-y

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