Molecular Mechanism of Surface-Assisted Self-Assembly of Amyloid-Like Peptides

Abstract

Peptide self-assembly attracted huge interests due to its clinical importance in protein-aggregation diseases, as well as potential applications for novel material design. Large efforts have been exerted on unraveling factors for the growth dynamics and morphologies. However, an intrinsic delicacy present in molecular systems and environmental elements, such as electrophysical properties of surface and solution, often results in controversy. Recently, a 9-residue long peptide designed from consensus sequences of amyloidogenic proteins was shown to assemble into a highly-ordered epitaxial structure on both hydrophilic mica and hydrophobic highly-oriented pyrolytic graphite (HOPG) surfaces but with very different morphologies: upright conformations on mica and lying-down on HOPG. Furthermore, with raised salt concentrations the peptides formed a highly-ordered multilayered nanofilaments at the mica/water interface in highly controllable fashion, which is unusual compared to uncontrollable, disordered, amorphous aggregates observed in other proteins in the similar condition. In our study, we investigated in molecular level details on how various environmental factors determine the peptide assemblies on mica and HOPG surfaces from their morphologies to the epitaxial growth mechanism, using atomistic molecular dynamics simulations. Firstly, not only surface polarity but also surface structure closely incorporate with individual peptide structure, as synergistically inducing a highly-optimized parallel β-stranded arrays on mica. Next, we showed that hydrophobic sidechain interaction indeed drives the longitudinal length growth of the assembly, while hydrophilic backbone hydrogen bonds rather control the transversal thickness. Finally, in raised salt concentration, we found that double-layered structures of all upright conformation are energetically favorable on mica but with anti-parallel β-stands for the upper layer, while the lower still in the parallel configuration, which again emphasizes the importance of environmental factors like contacting surface.