Recent far-reaching advances in synthetic biology have yielded exciting tools for the creation of new materials. Conversely, advances in the fundamental understanding of soft-condensed matter, polymers and biomaterials offer new avenues to extend the reach of synthetic biology. The broad and exciting range of possible applications have substantial implications to address grand challenges in health, biotechnology and sustainability. Despite the potentially transformative impact that lies at the interface of synthetic biology and biomaterials, the two fields have, so far, progressed mostly separately. This Perspective provides a review of recent key advances in these two fields, and a roadmap for collaboration at the interface between the two communities. We highlight the near-term applications of this interface to the development of hierarchically structured biomaterials, from bioinspired building blocks to ‘living’ materials that sense and respond based on the reciprocal interactions between materials and embedded cells.
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Meng, F. & Ellis, T. The second decade of synthetic biology: 2010–2020. Nat. Commun. 11, 5174 (2020).
Sedlmayer, F., Aubel, D. & Fussenegger, M. Synthetic gene circuits for the detection, elimination and prevention of disease. Nat. Biomed. Eng. 2, 399–415 (2018).
Kolar, K., Knobloch, C., Stork, H., Žnidarič, M. & Weber, W. OptoBase: a web platform for molecular optogenetics. ACS Synth. Biol. 7, 1825–1828 (2018).
Moon, T. S., Lou, C., Tamsir, A., Stanton, B. C. & Voigt, C. A. Genetic programs constructed from layered logic gates in single cells. Nature 491, 249–253 (2012).
Gao, X. J., Chong, L. S., Kim, M. S. & Elowitz, M. B. Programmable protein circuits in living cells. Science 361, 1252–1258 (2018).
Tang, W. & Liu, D. R. Rewritable multi-event analog recording in bacterial and mammalian cells. Science 360, eaap8992 (2018).
Aoki, S. K. et al. A universal biomolecular integral feedback controller for robust perfect adaptation. Nature 570, 533–537 (2019).
Toda, S., Blauch, L. R., Tang, S. K. Y., Morsut, L. & Lim, W. A. Programming self-organizing multicellular structures with synthetic cell-cell signaling. Science 361, 156–162 (2018).
Smanski, M. J. et al. Synthetic biology to access and expand nature’s chemical diversity. Nat. Rev. Microbiol. 14, 135–149 (2016).
Noireaux, V. & Liu, A. P. The new age of cell-free biology. Annu. Rev. Biomed. Eng. 22, 51–77 (2020).
Godino, E. et al. Cell-free biogenesis of bacterial division proto-rings that can constrict liposomes. Commun. Biol. 3, 539 (2020).
Garenne, D., Libchaber, A. & Noireaux, V. Membrane molecular crowding enhances MreB polymerization to shape synthetic cells from spheres to rods. Proc. Natl Acad. Sci. USA 117, 1902–1909 (2020).
Saleh, O. A., Jeon, B. J. & Liedl, T. Enzymatic degradation of liquid droplets of DNA is modulated near the phase boundary. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2001654117 (2020).
Sokolova, E. et al. Enhanced transcription rates in membrane-free protocells formed by coacervation of cell lysate. Proc. Natl Acad. Sci. USA 110, 11692–11697 (2013).
Green, L. N. et al. Autonomous dynamic control of DNA nanostructure self-assembly. Nat. Chem. 11, 510–520 (2019).
Efrat, Y., Tayar, A. M., Daube, S. S., Levy, M. & Bar-Ziv, R. H. Electric-field manipulation of a compartmentalized cell-free gene expression reaction. ACS Synth. Biol. 7, 1829–1833 (2018).
Dupin, A. & Simmel, F. C. Signalling and differentiation in emulsion-based multi-compartmentalized in vitro gene circuits. Nat. Chem. 11, 32–39 (2019).
Santorelli, M., Lam, C. & Morsut, L. Synthetic development: building mammalian multicellular structures with artificial genetic programs. Curr. Opin. Biotechnol. 59, 130–140 (2019).
Scheller, L., Strittmatter, T., Fuchs, D., Bojar, D. & Fussenegger, M. Generalized extracellular molecule sensor platform for programming cellular behavior article. Nat. Chem. Biol. 14, 723–729 (2018).
Rivière, I. & Sadelain, M. Chimeric antigen receptors: a cell and gene therapy perspective. Mol. Ther. 25, 1117–1124 (2017).
Stapornwongkul, K. S., de Gennes, M., Cocconi, L., Salbreux, G. & Vincent, J. P. Patterning and growth control in vivo by an engineered GFP gradient. Science 370, 321–327 (2020).
Huang, X. et al. DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation. Nat. Nanotecnol. 16, 214–223 (2021).
Nielsen, A. A. K. et al. Genetic circuit design automation. Science 352, aac7341 (2016).
Burger, B. et al. A mobile robotic chemist. Nature 583, 237–241 (2020).
Sanka, R., Lippai, J., Samarasekera, D., Nemsick, S. & Densmore, D. 3DμF—interactive design environment for continuous flow microfluidic devices. Sci. Rep. 9, 9166 (2019).
Zhang, J. et al. Combining mechanistic and machine learning models for predictive engineering and optimization of tryptophan metabolism. Nat. Commun. 11, 4880 (2020).
Waltemath, D. et al. The first 10 years of the international coordination network for standards in systems and synthetic biology (COMBINE). J. Integr. Bioinform. 17, 20200005 (2020).
Huebsch, N. & Mooney, D. J. Inspiration and application in the evolution of biomaterials. Nature 462, 426–432 (2009).
Dimarco, R. L. & Heilshorn, S. C. Multifunctional materials through modular protein engineering. Adv. Mater. 24, 3923–3940 (2012).
Chaudhuri, O., Cooper-White, J., Janmey, P. A., Mooney, D. J. & Shenoy, V. B. Effects of extracellular matrix viscoelasticity on cellular behaviour. Nature 584, 535–546 (2020).
Rodell, C. B. et al. Shear-thinning supramolecular hydrogels with secondary autonomous covalent crosslinking to modulate viscoelastic properties in vivo. Adv. Funct. Mater. 25, 636–644 (2015).
Baker, B. M. et al. Cell-mediated fibre recruitment drives extracellular matrix mechanosensing in engineered fibrillar microenvironments. Nat. Mater. 14, 1262–1268 (2015).
Griffin, D. R., Weaver, W. M., Scumpia, P. O., Di Carlo, D. & Segura, T. Accelerated wound healing by injectable microporous gel scaffolds assembled from annealed building blocks. Nat. Mater. 14, 737–744 (2015).
Skylar-Scott, M. A., Mueller, J., Visser, C. W. & Lewis, J. A. Voxelated soft matter via multimaterial multinozzle 3D printing. Nature 575, 330–335 (2019).
Guo, Z., Liu, H., Dai, W. & Lei, Y. Responsive principles and applications of smart materials in biosensing. Smart Mater. Med. 1, 54–65 (2020).
Hörner, M. et al. Phytochrome-based extracellular matrix with reversibly tunable mechanical properties. Adv. Mater. 31, e1806727 (2019).
de Almeida, P. et al. Cytoskeletal stiffening in synthetic hydrogels. Nat. Commun. 10, 609 (2019).
Rosales, A. M., Vega, S. L., DelRio, F. W., Burdick, J. A. & Anseth, K. S. Hydrogels with reversible mechanics to probe dynamic cell microenvironments. Angew. Chem. Int. Ed. 56, 12132–12136 (2017).
Badeau, B. A. & Deforest, C. A. Programming stimuli-responsive behavior into biomaterials. Annu. Rev. Biomed. Eng. 21, 241–265 (2019).
Chao, Y. & Shum, H. C. Emerging aqueous two-phase systems: from fundamentals of interfaces to biomedical applications. Chem. Soc. Rev. 49, 114–142 (2020).
Schuster, B. S. et al. Identifying sequence perturbations to an intrinsically disordered protein that determine its phase-separation behavior. Proc. Natl Acad. Sci. USA 117, 11421–11431 (2020).
Klein, I. A. et al. Partitioning of cancer therapeutics in nuclear condensates. Science 368, 1386–1392 (2020).
Champeau, M. et al. 4D printing of hydrogels: a review. Adv. Funct. Mater. 30, 1910606 (2020).
Cangialosi, A. et al. DNA sequence–directed shape change of photopatterned hydrogels via high-degree swelling. Science 357, 1126–1130 (2017).
Praetorius, F. et al. Biotechnological mass production of DNA origami. Nature 552, 84–87 (2017).
Barbee, M. H. et al. Protein-mimetic self-assembly with synthetic macromolecules. Macromolecules 54, 3585–3612 (2021).
Chan, D. et al. Combinatorial polyacrylamide hydrogels for preventing biofouling on implantable biosensors. Preprint at bioRxiv https://doi.org/10.1101/2020.05.25.115675 (2021).
Upadhya, R. et al. Automation and data-driven design of polymer therapeutics. Adv. Drug Deliv. Rev. 171, 1–28 (2021).
Wu, D. et al. Polymers with controlled assembly and rigidity made with click-functional peptide bundles. Nature 574, 658–662 (2019).
Seeman, N. C. & Sleiman, H. F. DNA nanotechnology. Nat. Rev. Mater. 3, 17068 (2017).
Buchberger, A., Simmons, C. R., Fahmi, N. E., Freeman, R. & Stephanopoulos, N. Hierarchical assembly of nucleic acid/coiled-coil peptide nanostructures. J. Am. Chem. Soc. 142, 1406–1416 (2020).
An, B. et al. Programming living glue systems to perform autonomous mechanical repairs. Matter 3, 2080–2092 (2020).
Keeble, A. H. & Howarth, M. Power to the protein: enhancing and combining activities using the Spy toolbox. Chem. Sci. 11, 7281–7291 (2020).
Nguyen, P. Q., Botyanszki, Z., Tay, P. K. R. & Joshi, N. S. Programmable biofilm-based materials from engineered curli nanofibres. Nat. Commun. 5, 4945 (2014).
Charrier, M. et al. Engineering the S-layer of Caulobacter crescentus as a foundation for stable, high-density, 2D living materials. ACS Synth. Biol. 8, 181–190 (2019).
Zhang, G., Johnston, T., Quin, M. B. & Schmidt-Dannert, C. Developing a protein scaffolding system for rapid enzyme immobilization and optimization of enzyme functions for biocatalysis. ACS Synth. Biol. 8, 1867–1876 (2019).
Shadish, J. A., Strange, A. C. & Deforest, C. A. Genetically encoded photocleavable linkers for patterned protein release from biomaterials. J. Am. Chem. Soc. 141, 15619–15625 (2019).
Heveran, C. M. et al. Engineered ureolytic microorganisms can tailor the morphology and nanomechanical properties of microbial-precipitated calcium carbonate. Sci. Rep. 9, 14721 (2019).
Heveran, C. M. et al. Biomineralization and successive regeneration of engineered living building materials. Matter 2, 481–494 (2020).
Nielsen, J. & Keasling, J. D. Engineering cellular metabolism. Cell 164, 1185–1197 (2016).
Gilbert, C. et al. Living materials with programmable functionalities grown from engineered microbial co-cultures. Nat. Mater. 20, 691–700 (2021).
Duro-Royo, J., Van Zak, J., Tai, Y. J., Ling, A. S. & Oxman, N. in Challenges for Technology Innovation: An Agenda for the Future (eds da Silva, F. M. et al.) Ch. 39 (CRC, 2017).
Sachdeva, G., Garg, A., Godding, D., Way, J. C. & Silver, P. A. In vivo co-localization of enzymes on RNA scaffolds increases metabolic production in a geometrically dependent manner. Nucleic Acids Res. 42, 9493–9503 (2014).
Park, S. J. et al. Phototactic guidance of a tissue-engineered soft-robotic ray. Science 353, 158–162 (2016).
Morsut, L. et al. Engineering customized cell sensing and response behaviors using synthetic Notch receptors. Cell 164, 780–791 (2016).
Schwarz, K. A., Daringer, N. M., Dolberg, T. B. & Leonard, J. N. Rewiring human cellular input–output using modular extracellular sensors. Nat. Chem. Biol. 13, 202–209 (2017).
Loebel, C., Mauck, R. L. & Burdick, J. A. Local nascent protein deposition and remodelling guide mesenchymal stromal cell mechanosensing and fate in three-dimensional hydrogels. Nat. Mater. 18, 883–891 (2019).
Ferreira, S. A. et al. Bi-directional cell–pericellular matrix interactions direct stem cell fate. Nat. Commun. 9, 4049 (2018).
Liu, H. et al. Bioenergetic-active materials enhance tissue regeneration by modulating cellular metabolic state. Sci. Adv. 6, 32232154 (2020).
Li, Y. C., Zhang, Y. S., Akpek, A., Shin, S. R. & Khademhosseini, A. 4D bioprinting: the next-generation technology for biofabrication enabled by stimuli-responsive materials. Biofabrication 9, 012001 (2017).
Nam, K. T. et al. Virus-enabled synthesis and assembly of nanowires for lithium ion battery electrodes. Science 312, 885–888 (2006).
Kan, A. & Joshi, N. S. Towards the directed evolution of protein materials. MRS Commun. 9, 441–455 (2019).
Green, M. L. et al. Fulfilling the promise of the materials genome initiative with high-throughput experimental methodologies. Appl. Phys. Rev. 4, 011105 (2017).
Algahtani, M. S. et al. High throughput screening for biomaterials discovery. J. Control. Release 190, 115–126 (2014).
Agresti, J. J. et al. Ultrahigh-throughput screening in drop-based microfluidics for directed evolution. Proc. Natl Acad. Sci. USA 107, 4004–4009 (2010).
Ma, F. et al. Efficient molecular evolution to generate enantioselective enzymes using a dual-channel microfluidic droplet screening platform. Nat. Commun. 9, 1030 (2018).
Liu, Y. et al. Machine learning in materials genome initiative: a review. J. Mater. Sci. Technol. 57, 113–122 (2020).
Voigt, C. A. Synthetic biology 2020–2030: six commercially-available products that are changing our world. Nat. Commun. 11, 6379 (2020).
Beal, J. & Rogers, M. Levels of autonomy in synthetic biology engineering. Mol. Syst. Biol. 16, e10019 (2020).
Stowers, R. S. et al. Matrix stiffness induces a tumorigenic phenotype in mammary epithelium through changes in chromatin accessibility. Nat. Biomed. Eng. 3, 1009–1019 (2019).
We thank all the participants of the second Square Table workshop during which the ideas in this Perspective originated. The workshop was funded by the National Science Foundation (NSF) grant BMAT-1939310. We especially acknowledge G. Iannacchione for his stewardship of the Square Table workshops. We also acknowledge support from the National Institutes of Health grants R01 EB030031 (A.P.L.), R35 GM138256 (L.M.), R21 CA232244 (K.H.), NSF grants CMMI 1846367 (O.C.), DMR-BMAT CAREER 1753387 (N.S.), EF-1934496 (V.N.), DMR-2004875 (N.S.J.), DMR-2004937 (M.T.V.), CBET-2033654 (B.M.B.), DMR-2037055 (S.L.V.), MCB-2033387 (S.K.Y.T.), DMR-2004796 (J.M.), DMR-2011824 (A.M.K.), the Human Frontiers in Science Program RGP0045/2018 (S.P.), Department of Energy grants DOE BES DE-SC-0010595 (E.F. and R.S.), DGF grant DFG-EXC-2189 (W.W.), Dutch Ministry of Education, Culture and Science—Gravitation 024.001.035 (P.H.J.K.) and the DARPA Engineered Living Materials Program (P.D.A.).
The authors declare no competing interests.
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Liu, A.P., Appel, E.A., Ashby, P.D. et al. The living interface between synthetic biology and biomaterial design. Nat. Mater. 21, 390–397 (2022). https://doi.org/10.1038/s41563-022-01231-3
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