(636e) Structural Evaluation of Designer Co-Assembling Peptide Nanofibers

Co-assembling peptides represent an emerging platform for preparing supramolecular biomaterials with desired structures and functions for various medical and biotechnology applications. Compared to self-assembly where peptide interactions with itself dictate assembly, co-assembly only occurs upon interaction between complementary peptide partners. Recently, two designer β-sheet-forming co-assembling pairs, CATCH(+)/CATCH(-) peptides developed by Seroski and Hudalla and KW(+)/KW(-) peptides designed by King and Webb, have been reported. Key to these co-assembling peptide designs is the principle of charge complementarity where a net positive or negative charge on each peptide molecule discourages self-assembly, but electrostatic interactions between oppositely-charged peptide strands allow for co-assembly. Prior biophysical measurements using Thioflavin T fluorimetry, circular dichroism, and FTIR spectroscopy suggest both peptide systems co-assemble into β-sheet peptide nanofibers. Here, we examine at a molecular-level the role of charge on nanofiber structure using coarse-grained molecular dynamics simulations and solid-state NMR measurements. Both experimental measurements and computational predictions support the hypothesis of molecular-level co-assembly with β-sheets predominantly comprised of alternating peptide strands. Surprisingly, coarse-grained MD simulations and dipolar recoupling NMR measurements indicate peptides with the same charge can be adjacent to each other to varying degrees. Through a variation in net peptide charge, we demonstrate the possibility to control the distribution of nearest neighbors within co-assembled β-sheet peptide nanofibers.