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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