Engineering Novel Self-Assembling Peptide Materials By Studying The Self-Assembly Of Diphenylalanine

Self-assembling peptides represent a new class of biocompatible, nanostructured materials with a vast array of applications. In particular, the recently-discovered diphenylalanine peptide (FF) self-assembles into nanotubes with remarkable properties: exceptional stability to heat and solvents, and high mechanical strength. Because FF nanotubes are environmentally-benign and inexpensive, quite naturally they have become attractive for a broad range of applications, from templating nanodevice structures as sacrificial scaffolds (e.g., nanowires and nanofluidic channels) to dramatically enhancing interfacial surface areas to improve supercacitors, biosensors, and super-hydrophobic technologies. While experiments have investigated the properties and applications of FF nanotubes, little is known about their self-assembly mechanism or the intermolecular interactions underlying their stability.

Here, we use atomic-resolution simulations of FF peptides to gain insight into the early stages of oligomerization and the driving forces for assembly.  Specifically, we use molecular dynamics simulations to characterize oligomers of FF peptides in aqueous solution. We measure contacts, dihedral angles, and structures, and compare to the putative experimental x-ray crystal structure of FF nanotubes. Our results suggest that both hydrophobic interactions between the phenylalanine side-chains and electrostatic interactions between their termini drive assembly of small oligomers, while hydrophobic interactions are more relevant for forming large scale structures (as seen through simulations of the crystal structure). We are now using these simulations to generate coarse-grained models capable of modeling larger self-assembly events that can identify mechanisms and driving forces for self-assembly. Ultimately, a deeper understanding of FF nanotube assembly should facilitate the functionalization and engineering of new synthetic peptide-based materials.