Solvent Effects on Kinetic Mechanisms of Self-Assembly by Peptide Amphiphiles via Molecular Dynamics Simulations

Peptide amphiphiles are known to form a variety of distinctive self-assembled nanostructures (including cylindrical nanofibers in hydrogels) dependent upon the solvent conditions. Using a novel coarse-grained model, large-scale molecular dynamics simulations are performed on a system of 800 peptide amphiphiles (sequence, palmitoyl-Val(3)Ala(3)Glu(3)) to elucidate kinetic mechanisms of molecular assembly as a function of the solvent conditions. The assembly process is found to occur via a multistep process with transient intermediates that ultimately leads to the stabilized nanostructures including open networks of beta-sheets, cylindrical nanofibers, and elongated micelles. Different kinetic mechanisms are compared in terms of peptide secondary structures, solvent-accessible surface area, radius of gyration, relative shape anisotropy, intra/intermolecular interactions, and aggregate size dynamics to provide insightful information for the design of functional biomaterials.