Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Rapid Communication
  • Published:

Design of gel-to-sol UCST transition peptides by controlling polypeptide β-sheet nanostructures

Polymer Journal volume 53, pages 943–949 (2021)Cite this article

Subjects

Abstract

Creating stimulus-responsive materials solely by controlling polypeptide secondary nanostructures is challenging. We synthesized a methyl poly(ethylene glycol)-b-poly(O-benzyl-L-threonine) (mPEG-PBnLT) diblock copolymer that exhibited gel-to-sol UCST (Upper Critical Solution Temperature) transition behavior in an aqueous solution. The transition temperature window was easily adjusted by changing the copolymer concentration or length of the PBnLT block. Disassembly of the initial β-sheet nanoassemblies caused nanofibril transformation to spherical aggregates with increasing temperature, resulting in a gel-to-sol UCST transition. This result inspires a brand-new strategy for the structural design and functional control of materials.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Scheme 1
Scheme 2
Fig. 1
Fig. 2
Fig. 3

References

  1. Martinek TA, Hetényi A, Fülöp L, Mándity IM, Tóth GK, Dékány I. et al. Secondary structure dependent self‐assembly of β‐peptides into nanosized fibrils and membranes.Angew Chem Int Ed. 2006;45:2396–400.

    Article  CAS  Google Scholar 

  2. Hoop CL, Zhu J, Bhattacharya S, Tobita CA, Radford SE, Baum J. CollagenI weakly interacts with the β-sheets of β2-microglobulin and enhances conformationalexchange to induce amyloid formation. J Am Chem Soc. 2020;142:1321–31.

    Article  CAS  PubMed  Google Scholar 

  3. Appella DH, Christianson LA, Klein DA, Powell DR, Huang XL, Barchi JJ. et al. Residue-basedcontrol of helix shape in β-peptide oligomers. Nature. 1997;387:381–4.

    Article  CAS  PubMed  Google Scholar 

  4. Seebach D, Abele S, Gademann K, Jaun B. Pleatedsheets and turns of β-peptides with proteinogenic side chains. Angew Chem Int Ed.1999;38:1595–7.

    Article  CAS  Google Scholar 

  5. Porter EA, Wang X, Lee HS, Weisblum B, Gellman SH. Non-haemolyticβ-amino-acid oligomers. Nature. 2000;404:565–565.

    Article  CAS  PubMed  Google Scholar 

  6. Cheng RP, Gellman SH, DeGrado WF. β-Peptides: from structure to function. Chem Rev. 2001;101:3219–32.

    Article  CAS  PubMed  Google Scholar 

  7. Chi X, Yu G, Shao L, Chen J, Huang F. Adual-thermoresponsive gemini-type supra-amphiphilic macromolecular[3] pseudorotaxanebased on pillar[10] arene/paraquat cooperative complexation. J Am Chem Soc. 2016;138:3168–74.

    Article  CAS  PubMed  Google Scholar 

  8. Fuentes E, Gerth M, Berrocal JA, Matera C, Gorostiza P, Voets IK. et al. Anazobenzene-based single-component supramolecular polymer responsive to multiplestimuli in water. J Am Chem Soc. 2020;142:10069–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hendrikse SIS, Su L, Hogervorst TP, Lafleur RPM, Lou X, Marel GAV. et al. Elucidatingthe ordering in self-assembled glycocalyx mimicking supramolecular copolymersin water. J Am Chem Soc. 2019;141:13877–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gao J, Zhan J, Yang Z. Enzyme‐instructedself‐assembly (EISA) and hydrogelation of peptides. Adv Mater. 2020;32:1805798

    Article  CAS  Google Scholar 

  11. Mozhdehi D, Luginbuhl KM, Simon JR, Dzuricky M, Berger R, Varol HS. et al. Geneticallyencoded lipid-polypeptide hybrid biomaterials that exhibittemperature-triggered hierarchical self-assembly. Nat Chem. 2018;10:496–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ariga K, Jia X, Song J, Hill JP, Leong DT, Jia Y. et al. Insidecover: synergistic N‐heterocyclic carbene/palladium‐catalyzed umpolung 1,4‐additionof aryl iodides to enals. Angew Chem Int Ed. 2020;59:2–25.

    Article  Google Scholar 

  13. Choi YY, Jeong Y, Joo MK, Jeong B. Reversethermal organogelation of poly(ethylene glycol)‐polypeptide diblock copolymersin chloroform. Macromol Biosci. 2009;9:869–74.

    Article  CAS  PubMed  Google Scholar 

  14. Roy D, Brooks WLA, Sumerlin BS. Newdirections in thermoresponsive polymers. Chem Soc Rev. 2013;42:7214–43.

    Article  CAS  PubMed  Google Scholar 

  15. Hu J, Liu S. Responsivepolymers for detection and sensing applications: current status and future developments. Macromolecules. 2010;43:8315–30.

    Article  CAS  Google Scholar 

  16. Stuart MAC, Huck WTS, Genzer J, Muller M, Ober C, Stamm M. et al. Emergingapplications of stimuli-responsive polymer materials. Nat Mater. 2010;9:101–13.

    Article  PubMed  Google Scholar 

  17. Cobo I, Li M, Sumerlin BS, Perrier S. Smarthybrid materials by conjugation of responsive polymers to biomacromolecules. Nat Mater. 2015;14:143–59.

    Article  CAS  PubMed  Google Scholar 

  18. Figg CA, Simula A, Gebre KA, Tucker BS, Haddleton DM, Sumerlin BS. Polymerization-inducedthermal self-assembly (PITSA). Chem Sci. 2015;6:1230–6.

    Article  CAS  PubMed  Google Scholar 

  19. Park MH, Joo MK, Choi BG, Jeong B. Dynamicsof water interacting with interfaces, molecules, and ions. Acc Chem Res. 2012;45:424–33.

    Article  CAS  PubMed  Google Scholar 

  20. Li M, He X, Ling Y, Tang H. Dual thermoresponsive homopolypeptide with LCST-type linkages and UCST-typependants: Synthesis, characterization, and thermoresponsive properties. Polymer. 2017;132:264–72.

    Article  CAS  Google Scholar 

  21. Halperin A, Kr€oger M, Winnik FM. Poly(N‐isopropylacrylamide)phase diagrams: Fifty years of research. Angew Chem Int Ed. 2015;54:15342–67.

    Article  CAS  Google Scholar 

  22. Niskanen J, Tenhu H. Howto manipulate the upper critical solution temperature (UCST)?. Polym Chem. 2017;8:220–32.

    Article  CAS  Google Scholar 

  23. Arotçarena M, Heise B, Ishaya S, Laschewsky A. Switchingthe inside and the outside of aggregates of water-soluble block copolymers withdouble thermoresponsivity. J Am Chem Soc. 2002;124:3787–93.

    Article  PubMed  Google Scholar 

  24. Virtanen J, Arotçarena M, Heise B, Ishaya S, Laschewsky A, Tenhu H. Dissolutionand aggregation of a poly(NIPA-block-sulfobetaine) copolymer in water and salineaqueous solutions. Langmuir. 2002;18:5360–5.

    Article  CAS  Google Scholar 

  25. Dai F, Wang P, Wang Y, Tang L, Yang J, Liu W. et al. Doublethermoresponsive polybetaine-based ABA triblock copolymers with capability tocondense DNA. Polymer. 2008;49:5322–8.

    Article  CAS  Google Scholar 

  26. Guo H, Mussault C, Marcellan A. et al. Hydrogels with dual thermoresponsive mechanical performance. Macromol Rapid Commun. 2017;38:1700287.

    Article  Google Scholar 

  27. Hildebrand V, Heydenreich M, Laschewsky A, M€oller HM, Müller-Buschbaum P, Papadakis CM. et al. “Schizophrenic” self-assembly of dual thermoresponsive block copolymers bearing a zwitterionicand a non-ionic hydrophilic block. Polymer. 2017;122:347–57.

    Article  CAS  Google Scholar 

  28. Bera S, Mondal S, Xue B, Shimo LJW, Cao Y, Gazit E. Rigidhelical-like assemblies from a self-aggregating tripeptide. Nat Mater. 2019;18:503–9.

    Article  CAS  PubMed  Google Scholar 

  29. Gibson MI, Cameron NR. Organogelationof sheet-helix diblock copolypeptides. Angew Chem Int Ed. 2008;47:5160–2.

    Article  CAS  Google Scholar 

  30. Roberts MJ, Bentley MD, Harris JM. Chemistry for peptideand protein PEGylation. Adv Drug Deliv Rev. 2012;64S:116–27.

    Article  Google Scholar 

  31. Gong CY, Shi S, Dong PW. et al. Synthesis andcharacterization of PEG-PCL-PEG thermosensitive hydrogel. Int J Pharm. 2009;365:89–99.

    Article  CAS  PubMed  Google Scholar 

  32. Shinde UP, Moon HJ, Ko DY, Jung BK, Jeong B. Control of rhGH release profilefrom PEG-PAF thermogel. Biomacromolecules. 2015;16:1461–69.

    Article  CAS  PubMed  Google Scholar 

  33. Deng C, Wu J, Cheng R, Meng F, Klok H, Zhong Z. Functional polypeptide andhybrid materials: Precision synthesis via α-amino acid N-carboxyanhydridepolymerization and emerging biomedical applications. Prog Polym Sci. 2014;39:330–64.

    Article  CAS  Google Scholar 

  34. Iyer A, Roeters SJ, Kogan V, Woutersen S, Claessens MMAE, Subramaniam V. Secondary structure effectof polypeptide on reverse thermal gelation and degradation of l/dl-poly(alanine)-poloxamer-l/dl-poly(alanine)copolymers. J Am Chem Soc. 2017;139:15392–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Huang K-Y, Yu C-C, Horng J-C. C-Terminal truncatedα-synuclein fibrils contain strongly twisted β-sheets. Biomacromolecules. 2020;21:1195–201.

    Article  CAS  PubMed  Google Scholar 

  36. Clarke DE, Pashuck ET, Bertazzo S, Weaver JVM, Stevens MM. Conjugating catalyticpolyproline fragments with a self-assembling peptide produces efficient artificialhydrolases. J Am Chem Soc. 2017;139:7250–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gao J, Tang C, Elsawy MA, Smith AM, Miller AF, Saiani A. Self-healing,self-assembled β-sheet peptide-poly(γ-glutamic acid) hybrid hydrogels. Biomacromolecules. 2017;18:826–34.

    Article  CAS  PubMed  Google Scholar 

  38. Pauling LR, Corey B. Controlling self-assemblingpeptide hydrogel properties through network topology. Proc R Soc B: Biol Sci. 1953;141:21–33.

    CAS  Google Scholar 

  39. Jeong Y, Joo MK, Bahk KH, Choi YY, Kim H-T, Kim W-K. et al. Stableconfigurations of polypeptide chains. J Controlled Release. 2009;137:25–30.

    Article  CAS  Google Scholar 

  40. Oh HJ, Joo MK, Sohn YS, Jeong B. Enzymaticallydegradable temperature-sensitive polypeptide as a new in-situ gellingbiomaterial. Macromolecules. 2008;41:8204–9.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the National Natural Sciences Fund of China (No. 31670979 and 51273034) and the Science and Technology Program of Sichuan Province (2019YFS0132).

Author information

Authors and Affiliations

  1. School of Materials and Energy, University of Electronic Science and Technology of China, Chengdu, China

    Hongyu Zhu, Dongxu Gu, Zikun Rao, Yang Li, Yu Liu & Jianyuan Hao

Authors
  1. Hongyu Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dongxu Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zikun Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yu Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jianyuan Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jianyuan Hao.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhu, H., Gu, D., Rao, Z. et al. Design of gel-to-sol UCST transition peptides by controlling polypeptide β-sheet nanostructures. Polym J 53, 943–949 (2021). https://doi.org/10.1038/s41428-021-00490-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41428-021-00490-2

This article is cited by

Search

Advanced search

Quick links