Xu, H (reprint author), China Univ Petr East China, Ctr Bioengn & Biotechnol, Qingdao 266580, Peoples R China.
; Wang, YT (reprint author), Chinese Acad Sci, Inst Theoret Phys, Key Lab Theoret Phys, Beijing 100190, Peoples R China.
; Wang, YT (reprint author), Univ Chinese Acad Sci, Sch Phys Sci, Beijing 100049, Peoples R China.
Besides our previous experimental discovery (Zhao Y R, et al. 2015 Langmuir, 31, 12975) that acetonitrile (ACN) can tune the morphological features of nanostructures self-assembled by short peptides KIIIIK (KI4K) in aqueous solution, further experiments reported in this work demonstrate that ACN can also tune the mass of the self-assembled nanostructures. To understand the microscopic mechanism how ACN molecules interfere peptide self-assembly process, we conducted a series of molecular dynamics simulations on a monomer, a cross-beta sheet structure, and a proto-fibril of KI4K in pure water, pure ACN, and ACN-water mixtures, respectively. The simulation results indicate that ACN enhances the intra-sheet interaction dominated by the hydrogen bonding (H-bonding) interactions between peptide backbones, but weakens the inter-sheet interaction dominated by the interactions between hydrophobic side chains. Through analyzing the correlations between different groups of solvent and peptides and the solvent behaviors around the proto-fibril, we have found that both the polar and nonpolar groups of ACN play significant roles in causing the opposite effects on intermolecular interactions among peptides. The weaker correlation of the polar group of ACN than water molecule with the peptide backbone enhances H-bonding interactions between peptides in the proto-fibril. The stronger correlation of the nonpolar group of ACN than water molecule with the peptide side chain leads to the accumulation of ACN molecules around the proto-fibril with their hydrophilic groups exposed to water, which in turn allows more water molecules close to the proto-fibril surface and weakens the inter-sheet interactions. The two opposite effects caused by ACN form a microscopic mechanism clearly explaining our experimental observations.
National Basic Research Program of China [2013CB932804]
; National Natural Science Foundation of China [91227115, 11421063, 11504431, 21503275]
; Fundamental Research Funds for Central Universities of China [15CX02025A]
; Application Research Foundation for Post-doctoral Scientists of Qingdao City, China [T1404096]