Aggregation-Induced Asymmetric Charge States of Amino Acids in Supramolecular Nanofibers

Electrostatic interactions contribute critically to the kinetic pathways and thermodynamic outcomes of peptide self-assembly involving one or more than one charged amino acids. While it is well understood in protein folding that those amino acids with acidic/basic side chains could shift their pK_as when placed in a hydrophobic microenvironment, to what extent aggregation of monomeric peptide units from the bulk solution could alter their charged status and how this change in pK_a values would reciprocally impact their assembly outcomes. Here, we design and analyze two solution systems containing peptide amphiphiles with hydrocarbon chains of different lengths to determine the factor of deprotonation on assembly. Our results suggest that models of supramolecular nanofibers with uniformly distributed, fully charged amino acids are oversimplified. We demonstrate, with molecular dynamics simulations, and validate with experimental results that asymmetric, different protonation states of the peptides lead to distinct nanostructures after self-assembly. The results give estimates on the electrostatic interactions in peptide amphiphiles required for their self-assembly and shed light on modeling molecular assembly systems containing charged amino acids.