Anisotropic formation mechanism and nanomechanics for the self-assembly process of cross- β peptides

Abstract

Nanostructures self-assembled by cross-β peptides with ordered structures and advantageous mechanical properties have many potential applications in biomaterials and nanotechnologies. Quantifying the intra-and inter-molecular driving forces for peptide self-assembly at the atomistic level is essential for understanding the formation mechanism and nanomechanics of various morphologies of self-assembled peptides. We investigate the thermodynamics of the intra-and inter-sheet structure formations in the self-assembly process of cross-β peptide KIIIIK by means of steered molecular dynamics simulation combined with umbrella sampling. It is found that the mechanical properties of the intra-and inter-sheet structures are highly anisotropic with their intermolecular bond stiffness at the temperature of 300 K being 5.58 N/m and 0.32 N/m, respectively. This mechanical anisotropy comes from the fact that the intra-sheet structure is stabilized by enthalpy but the inter-sheet structure is stabilized by entropy. Moreover, the formation process of KIIIIK intra-sheet structure is cooperatively driven by the van der Waals (VDW) interaction between the hydrophobic side chains and the electrostatic interaction between the hydrophilic backbones, but that of the inter-sheet structure is primarily driven by the VDW interaction between the hydrophobic side chains. Although only peptide KIIIIK is studied, the qualitative conclusions on the formation mechanism should also apply to other cross-β peptides.

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“…Since the strength of van der Waals forces is weaker than that of hydrogen bonds, it rarely acts as the main force to promote peptide self-assembly, but always cooperates with other interactions as a driver. Wang and colleages utilized steered molecular dynamics (MD) simulations and umbrella sampling techniques to investigate the formation mechanism of KIIIIK in their study 90 . The findings revealed that the formation of the intra-sheet structure was influenced by both van der Waals and electrostatic interactions, whereas the inter-sheet structure was mainly governed by the van der Waals force.…”