Control over the fibrillization yield by varying the oligomeric nucleation propensities of self-assembling peptides

Chun Yin Jerry Lau; Federico Fontana; Laurens D.B. Mandemaker; Dennie Wezendonk; Benjamin Vermeer; Alexandre M.J.J. Bonvin; Renko de Vries; Heyang Zhang; Katrien Remaut; Joep van den Dikkenberg; João Medeiros-Silva; Alia Hassan; Barbara Perrone; Rainer Kuemmerle; Fabrizio Gelain; Wim E. Hennink; Markus Weingarth; Enrico Mastrobattista

doi:10.1038/s42004-020-00417-7

Control over the fibrillization yield by varying the oligomeric nucleation propensities of self-assembling peptides

Chun Yin Jerry Lau, Federico Fontana, Laurens D.B. Mandemaker, Dennie Wezendonk, Benjamin Vermeer, Alexandre M.J.J. Bonvin, Renko de Vries, Heyang Zhang, Katrien Remaut, Joep van den Dikkenberg, João Medeiros-Silva, Alia Hassan, Barbara Perrone, Rainer Kuemmerle, Fabrizio Gelain, Wim E. Hennink, Markus Weingarth, Enrico Mastrobattista

IRCCS Casa Sollievo della Sofferenza

Research output: Contribution to journal › Article › peer-review

Abstract

Self-assembling peptides are an exemplary class of supramolecular biomaterials of broad biomedical utility. Mechanistic studies on the peptide self-assembly demonstrated the importance of the oligomeric intermediates towards the properties of the supramolecular biomaterials being formed. In this study, we demonstrate how the overall yield of the supramolecular assemblies are moderated through subtle molecular changes in the peptide monomers. This strategy is exemplified with a set of surfactant-like peptides (SLPs) with different β-sheet propensities and charged residues flanking the aggregation domains. By integrating different techniques, we show that these molecular changes can alter both the nucleation propensity of the oligomeric intermediates and the thermodynamic stability of the fibril structures. We demonstrate that the amount of assembled nanofibers are critically defined by the oligomeric nucleation propensities. Our findings offer guidance on designing self-assembling peptides for different biomedical applications, as well as insights into the role of protein gatekeeper sequences in preventing amyloidosis.

Original language	English
Article number	164
Journal	Communications Chemistry
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s42004-020-00417-7
Publication status	Published - Dec 2020

ASJC Scopus subject areas

Chemistry(all)
Materials Chemistry
Environmental Chemistry
Biochemistry

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10.1038/s42004-020-00417-7

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Lau, C. Y. J., Fontana, F., Mandemaker, L. D. B., Wezendonk, D., Vermeer, B., Bonvin, A. M. J. J., de Vries, R., Zhang, H., Remaut, K., van den Dikkenberg, J., Medeiros-Silva, J., Hassan, A., Perrone, B., Kuemmerle, R., Gelain, F., Hennink, W. E., Weingarth, M., & Mastrobattista, E. (2020). Control over the fibrillization yield by varying the oligomeric nucleation propensities of self-assembling peptides. Communications Chemistry, 3(1), [164]. https://doi.org/10.1038/s42004-020-00417-7

Lau, CYJ, Fontana, F, Mandemaker, LDB, Wezendonk, D, Vermeer, B, Bonvin, AMJJ, de Vries, R, Zhang, H, Remaut, K, van den Dikkenberg, J, Medeiros-Silva, J, Hassan, A, Perrone, B, Kuemmerle, R, Gelain, F, Hennink, WE, Weingarth, M & Mastrobattista, E 2020, 'Control over the fibrillization yield by varying the oligomeric nucleation propensities of self-assembling peptides', Communications Chemistry, vol. 3, no. 1, 164. https://doi.org/10.1038/s42004-020-00417-7

@article{7dc54ac740974468b2259c4b384c31be,

title = "Control over the fibrillization yield by varying the oligomeric nucleation propensities of self-assembling peptides",

abstract = "Self-assembling peptides are an exemplary class of supramolecular biomaterials of broad biomedical utility. Mechanistic studies on the peptide self-assembly demonstrated the importance of the oligomeric intermediates towards the properties of the supramolecular biomaterials being formed. In this study, we demonstrate how the overall yield of the supramolecular assemblies are moderated through subtle molecular changes in the peptide monomers. This strategy is exemplified with a set of surfactant-like peptides (SLPs) with different β-sheet propensities and charged residues flanking the aggregation domains. By integrating different techniques, we show that these molecular changes can alter both the nucleation propensity of the oligomeric intermediates and the thermodynamic stability of the fibril structures. We demonstrate that the amount of assembled nanofibers are critically defined by the oligomeric nucleation propensities. Our findings offer guidance on designing self-assembling peptides for different biomedical applications, as well as insights into the role of protein gatekeeper sequences in preventing amyloidosis.",

author = "Lau, {Chun Yin Jerry} and Federico Fontana and Mandemaker, {Laurens D.B.} and Dennie Wezendonk and Benjamin Vermeer and Bonvin, {Alexandre M.J.J.} and {de Vries}, Renko and Heyang Zhang and Katrien Remaut and {van den Dikkenberg}, Joep and Jo{\~a}o Medeiros-Silva and Alia Hassan and Barbara Perrone and Rainer Kuemmerle and Fabrizio Gelain and Hennink, {Wim E.} and Markus Weingarth and Enrico Mastrobattista",

note = "Funding Information: C.Y.J.L. acknowledges the support from the European Union (Horizion 2020 NANOMED Grant 676137). We thank Lione Willems (Wageningen University, The Netherlands) for her support in AFM and the Netherlands Center for Multiscale Catalytic Energy conversion (MCEC), an NWO Gravitation program funded by the Ministry of Education, Culture and Science of the government of The Netherlands, for the financial support with the AFM measurements; Javier Sastre Tora{\~n}o (Utrecht University, The Netherlands) for his support in ESI-MS. Kevin Braeckmans (Ghent University, Belgium) for his advice on MEM analysis. M.W. acknowledges financial support (project numbers 723.014.003 and 711.018.001) from the Dutch Research Council (NWO). F.F. and F.G. acknowledge the support from the Italian Ministry of Health (Ricerca Corrente 2018–2020). The secondment of F.F. at Utrecht University was granted by the Erasmus Traineeship Program of University of Milano-Bicocca. We thank Professor Dr. Alexander Kros (Leiden University, The Netherlands) for critically reviewing this manuscript before submitting it for publication. Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = dec,

doi = "10.1038/s42004-020-00417-7",

language = "English",

volume = "3",

journal = "Communications Chemistry",

issn = "2399-3669",

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T1 - Control over the fibrillization yield by varying the oligomeric nucleation propensities of self-assembling peptides

AU - Lau, Chun Yin Jerry

AU - Fontana, Federico

AU - Mandemaker, Laurens D.B.

AU - Wezendonk, Dennie

AU - Vermeer, Benjamin

AU - Bonvin, Alexandre M.J.J.

AU - de Vries, Renko

AU - Zhang, Heyang

AU - Remaut, Katrien

AU - van den Dikkenberg, Joep

AU - Medeiros-Silva, João

AU - Hassan, Alia

AU - Perrone, Barbara

AU - Kuemmerle, Rainer

AU - Gelain, Fabrizio

AU - Hennink, Wim E.

AU - Weingarth, Markus

AU - Mastrobattista, Enrico

N1 - Funding Information: C.Y.J.L. acknowledges the support from the European Union (Horizion 2020 NANOMED Grant 676137). We thank Lione Willems (Wageningen University, The Netherlands) for her support in AFM and the Netherlands Center for Multiscale Catalytic Energy conversion (MCEC), an NWO Gravitation program funded by the Ministry of Education, Culture and Science of the government of The Netherlands, for the financial support with the AFM measurements; Javier Sastre Toraño (Utrecht University, The Netherlands) for his support in ESI-MS. Kevin Braeckmans (Ghent University, Belgium) for his advice on MEM analysis. M.W. acknowledges financial support (project numbers 723.014.003 and 711.018.001) from the Dutch Research Council (NWO). F.F. and F.G. acknowledge the support from the Italian Ministry of Health (Ricerca Corrente 2018–2020). The secondment of F.F. at Utrecht University was granted by the Erasmus Traineeship Program of University of Milano-Bicocca. We thank Professor Dr. Alexander Kros (Leiden University, The Netherlands) for critically reviewing this manuscript before submitting it for publication. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/12

Y1 - 2020/12

N2 - Self-assembling peptides are an exemplary class of supramolecular biomaterials of broad biomedical utility. Mechanistic studies on the peptide self-assembly demonstrated the importance of the oligomeric intermediates towards the properties of the supramolecular biomaterials being formed. In this study, we demonstrate how the overall yield of the supramolecular assemblies are moderated through subtle molecular changes in the peptide monomers. This strategy is exemplified with a set of surfactant-like peptides (SLPs) with different β-sheet propensities and charged residues flanking the aggregation domains. By integrating different techniques, we show that these molecular changes can alter both the nucleation propensity of the oligomeric intermediates and the thermodynamic stability of the fibril structures. We demonstrate that the amount of assembled nanofibers are critically defined by the oligomeric nucleation propensities. Our findings offer guidance on designing self-assembling peptides for different biomedical applications, as well as insights into the role of protein gatekeeper sequences in preventing amyloidosis.

AB - Self-assembling peptides are an exemplary class of supramolecular biomaterials of broad biomedical utility. Mechanistic studies on the peptide self-assembly demonstrated the importance of the oligomeric intermediates towards the properties of the supramolecular biomaterials being formed. In this study, we demonstrate how the overall yield of the supramolecular assemblies are moderated through subtle molecular changes in the peptide monomers. This strategy is exemplified with a set of surfactant-like peptides (SLPs) with different β-sheet propensities and charged residues flanking the aggregation domains. By integrating different techniques, we show that these molecular changes can alter both the nucleation propensity of the oligomeric intermediates and the thermodynamic stability of the fibril structures. We demonstrate that the amount of assembled nanofibers are critically defined by the oligomeric nucleation propensities. Our findings offer guidance on designing self-assembling peptides for different biomedical applications, as well as insights into the role of protein gatekeeper sequences in preventing amyloidosis.

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ER -

Control over the fibrillization yield by varying the oligomeric nucleation propensities of self-assembling peptides

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