(634b) Sequence-Dependent Self-Assembly of Peptide Amphiphiles Via Molecular Simulations

Stimulus-responsive biomaterials have been of great interest for a wide range of therapeutic applications including the design of biomimetic tissue scaffolds and drug delivery systems. Peptide amphiphiles (PAs), which are comprised of a bioactive peptide sequence that is chemically conjugated to a hydrophobic alkyl tail, have been shown to undergo self-assembly to form nanostructures (e.g., cylindrical nanofibers, spherical micelles) whose morphology is strongly dependent upon the solvent condition. In this study, we investigate a series of PAs to examine the effect of peptide sequence on self-assembly behavior and morphological properties of stimuli-responsive nanostructures via molecular simulations. Implementation of a newly extended intermediate-resolution protein model coupled with discrete molecular dynamics simulation technique enables the simulation of large PA systems to observe the whole self-assembly process. This allows us to elucidate kinetic mechanisms of self-assembly to form cylindrical nanofibers and spherical micelles as a function of the pH condition.  Moreover, placing nonpolar peptide residues adjacent to the alkyl tail causes them to experience a nanofiber-to-micelle transition as a function of decreased pH values due to the close proximity of charged residues. By manipulating the placement of peptide residues, the intermolecular interactions involved can ultimately be controlled and used as an effective parameter to design smart biomaterials.