The Supramolecular Organization of a Peptide-Based Nanocarrier at High Molecular Detail

Mazda Radmalekshahi, Koen M. Visscher, João Garcia Lopes Maia Rodrigues, Renko De Vries, Wim E. Hennink, Marc Baldus, Alexandre M J J Bonvin*, Enrico Mastrobattista, Markus Weingarth

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Nanovesicles self-assembled from amphiphilic peptides are promising candidates for applications in drug delivery. However, complete high-resolution data on the local and supramolecular organization of such materials has been elusive thus far, which is a substantial obstacle to their rational design. In the absence of precise information, nanovesicles built of amphiphilic "lipid-like" peptides are generally assumed to resemble liposomes that are organized from bilayers of peptides with a tail-to-tail ordering. Using the nanocarrier formed by the amphiphilic self-assembling peptide 2 (SA2 peptide) as an example, we derive the local and global organization of a multimega-Dalton peptide-based nanocarrier at high molecular detail and at close-to physiological conditions. By integrating a multitude of experimental techniques (solid-state NMR, AFM, SLS, DLS, FT-IR, CD) with large- and multiscale MD simulations, we show that SA2 nanocarriers are built of interdigitated antiparallel β-sheets, which bear little resemblance to phospholipid liposomes. Our atomic level study allows analyzing the vesicle surface structure and dynamics as well as the intermolecular forces between peptides, providing a number of potential leads to improve and tune the biophysical properties of the nanocarrier. The herein presented approach may be of general utility to investigate peptide-based nanomaterials at high-resolution and at physiological conditions. (Figure Presented).

Original languageEnglish
Pages (from-to)7775-7784
Number of pages10
JournalJournal of the American Chemical Society
Volume137
Issue number24
DOIs
Publication statusPublished - 24 Jun 2015

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