title: The Supramolecular Organization of a Peptide-Based Nanocarrier at High Molecular Detail.
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.
authors.affiliation: ‡Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
authors.forename: Mazda
authors.initials: M
authors.lastname: Rad-Malekshahi
authors.affiliation: †NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Koen M
authors.initials: KM
authors.lastname: Visscher
authors.affiliation: †NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: João P G L M
authors.initials: JP
authors.lastname: Rodrigues
authors.affiliation: §Laboratory of Physical Chemistry and Colloid Science, Wageningen University, Dreijenplein 6, 6703 HB Wageningen, The Netherlands.
authors.forename: Renko
authors.initials: R
authors.lastname: de Vries
authors.affiliation: ‡Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.affiliation: †NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Baldus
authors.affiliation: †NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
authors.affiliation: ‡Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
authors.forename: Enrico
authors.initials: E
authors.lastname: Mastrobattista
authors.affiliation: †NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Markus
authors.initials: M
authors.lastname: Weingarth
mesh_terms: D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D053769:Nanocapsules; D010455:Peptides; D013501:Surface-Active Agents