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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-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 languageEnglish
Article number164
JournalCommunications Chemistry
Volume3
DOIs
Publication statusPublished - 11 Nov 2020

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