388731 Invited Talk: Multi-Scale Modeling of the pH-Controlled Self-Assembly By Peptide Amphiphiles

Monday, November 17, 2014: 12:30 PM
Crystal Ballroom A/F (Hilton Atlanta)
Iris W. Fu and Hung D. Nguyen, Department of Chemical Engineering and Materials Science, University of California, Irvine, Irvine, CA

Self-assembling nanomaterials that can change shape or structure in response to environmental stimuli hold a great promise to revolutionize medicine and biotechnology. However, current discovery is slow and often serendipitous; therefore, there is a great need in detailed, predictive modeling. Here we report a multi-scale modeling study based on two state-of-the-art techniques to elucidate pH-dependent morphological transition between spherical micelles and cylindrical nanofibers that are self-assembled from peptide amphiphiles (PA), palmitoyl-I-A3E4-NH2. The coarse-grained molecular dynamics simulations revealed that self-assembly of spherical micelles is driven by hydrophobic interactions between alkyl tails when the electrostatic repulsion is strong. Merging of these micelles into nanofibers is driven by β-sheet formation between the peptide segments when the electrostatic repulsion is weak. The all-atom constant pH molecular dynamics simulations revealed a cooperative transition between random coil (as exhibited in micelles) and β-sheet (as exhibited in nanofibers) in the pH range 6–7, in agreement with experiment. Interestingly, although the bulk pKa is more than one unit below the transition pH, consistent with experiment, the highest pKa’s coincide with the transition pH, suggesting that the latter may be tuned by modulating the pKa’s of a few solvent-buried Glu sidechains. Taken together, the present study illustrates a multiscale modeling strategy that may aid in the design and discovery of pH-responsive nanomaterials.

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