Synthetic, Extracellular Matrix Mimicking Hydrogel to Promote Spreading, Migration, and Proliferation of Schwann Cells

Peptide amphiphiles, short peptide sequences attached to a fatty acid tails, can self assemble into extended cylindrical micelles which entangle giving rise to a flexible hydrogel. The modular nature of peptide amphiphiles allows incorporation of features which can stabilize extended micelle structures, and add a variety of bioactive modalities. Here we present a peptide amphiphile system where hydrogen bonding of the peptide headgroup was studied as a method of stabilizing the self assembled micelle structure and thus increasing the modulus. Initially the solution behaves as a weak gel at acidic conditions, and then effectively crosslinks through amino acid side chain hydrogen bonding to form very stiff gels at physiological pH. Tuning of the modulus was accomplished by increasing the concentration and is able to span a range of G'= 100-10,000 Pa. Stiffness of the bulk material was also tuned independently of fiber density by changing the linker chemistry of the peptide headgroup. Using this versatile 3D system we were able to study a variety of applications where stiffness and ligand presentation must be tuned independently. One such application, nerve tissue regeneration, will be discussed where Schwann cells, a cell type involved in nerve tissue regeneration, are shown to sense stiffness changes in the underlying matrix, as evidence by changes in proliferation, spreading and migration.