(165e) Engineering Amyloid Inspired Peptide Nanofibers for Tunable Co-Assembly

Seren Hamsici,^* Andrew D. White,^# and Handan Acar^*

*University of Oklahoma, Stephenson School of Biomedical Engineering, Norman, OK, United States

^#University of Rochester, Department of Chemical Engineering, Rochester, NY, United States

Amyloid proteins have provided inspiration for developing functional materials due to their stability against mechanical, thermal and chemical factors. These amyloid based assemblies allow scientist to mimic the nature of amyloid structures to build amyloid inspired hierarchical synthetic structures for different applications such as drug delivery, tissue engineering and energy-based materials. The stability of Aß (1-42) was mainly derived from two different interactions which are salt bridges and hydrophobic clusters found in the core of protein. However, there is not still any general rule or method to understand the assembly kinetics and screen intermolecular interactions. In this research, we aim to present a simplistic tool consisting of oppositely charged hexapeptide to identify the effect of hydrophobicity and salt-bridges on aggregation kinetics and physical properties of final material such as secondary structures and mechanical properties. The design of hexapeptides was consisted of three different domains; i. diphenylalanine domain (a core recognition domain of ß-amyloid protein), charged domain at both N- and C- terminus and a substitution domain which are dialanine, ditryptophan and diisoleucine (Figure 1). By using both computational and experimental approaches, we observed that salt bridges are required for peptide fibrillization and the distance of undistrupted hydrophobic core in co-assembly has a strong effect on assembly kinetics, overall stability, fibrillar morphology, mechanical properties and structural organization.

Figure 1. Schematic description of peptide co-assembly triggered by oppositely charged hexapeptides. E and K residues at both ends provided electrostatic interactions, FF at the core contributed self-assembly with π-π stacking and replacing XX with either dialanine, ditrytophan or diisoleucine enabled tunable hydrophobic interactions