Nonionic peptide amphiphiles and their supramolecular co-assemblies tune charge density and bioactivity

Abstract

Supramolecular peptide assemblies generally rely on ionic groups for solubility in aqueous media but charge may sometimes affect their biological functions. Cationic residues in these assemblies are often associated with cell toxicity, and charged amino acids lead to supramolecular structures that are dependent on both pH and ionic strength. We report here on the synthesis of a nonionic peptide amphiphile (PA) containing a decaethylene glycol segment and its supramolecular co-assembly with ionic PA monomers as a strategy to produce uncharged assemblies and to fine tune charge density. We show that while morphology and internal structure depend on counterion screening and on pH for charged PA assemblies, these nonionic molecules self-assemble to form high-aspect ratio filaments containing β-sheets stable with or without ion screening and at acidic, neutral, and basic pH. By co-assembling nonionic PA molecules with charged PA molecules, we could produce supramolecular copolymers with tunable surface charge density, yet with stronger internal order than either fully charged or fully uncharged assemblies. Using an in vitro model for osteogenic differentiation of mesenchymal stem cells, we found that supramolecular assemblies containing nonionic molecules or co-assemblies of both nonionic and ionic PA molecules exhibit greater bioactivity than assemblies containing only charged molecules. We hypothesize that the enhanced bioactivity originates in the synergy between protein binding by PA molecules and increased supramolecular dynamics introduced by the nonionic ethylene glycol segments. Thus, nonionic PAs and their co-assemblies can be used to investigate how charge density and other factors affect bioactivity of water-soluble supramolecular nanostructures.