Biophysical Society Thematic Meeting - October 25-30, 2015

Polymers and Self Assembly: From Biology to Nanomaterials Poster Session I

48-POS

Board 48

The Supramolecular Organization of a Peptide-Based Nanocarrier at High-Resolution Mazda Rad-Malekshahi 2 , Koen M. Visscher 1 , Joao Rodrigues 1 , Renko De Vries 3 , Wim E. Hennink 2 , Marc Baldus 1 , Alexandre Bonvin 1 , Enrico Mastrobattista 2 , Markus Weingarth 1 . 1 Utrecht University, Utrecht, Netherlands, 2 Utrecht University, Utrecht, Netherlands, 3 Wageningen University, Wageningen, Netherlands. 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-resolution and at close-to physiological conditions. 1 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 and 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 is of general utility to investigate peptide-based nanomaterials at high-resolution and at physiological conditions, an important advance towards the tailoring of such materials for medial applications. 1. M. Rad-Malekshahi, K.M. Visscher, J.P.G.L.M. Rodrigues, R. de Vries, W.E. Hennink, M. Baldus, A.M.J.J. Bonvin, E. Mastrobattista, M. Weingarth, J. Am. Chem. Soc., in press, DOI: 10.1021/jacs.5b02919, The Supramolecular Organization of a Peptide-Based Nanocarrier at High Molecular Detail

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