TY - JOUR
T1 - The Supramolecular Organization of a Peptide-Based Nanocarrier at High Molecular Detail
AU - Radmalekshahi, Mazda
AU - Visscher, Koen M.
AU - Garcia Lopes Maia Rodrigues, João
AU - De Vries, Renko
AU - Hennink, Wim E.
AU - Baldus, Marc
AU - Bonvin, Alexandre M J J
AU - Mastrobattista, Enrico
AU - Weingarth, Markus
PY - 2015/6/24
Y1 - 2015/6/24
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=84932606718&partnerID=8YFLogxK
U2 - 10.1021/jacs.5b02919
DO - 10.1021/jacs.5b02919
M3 - Article
AN - SCOPUS:84932606718
SN - 0002-7863
VL - 137
SP - 7775
EP - 7784
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 24
ER -