title: Dewetting transitions in the self-assembly of two amyloidogenic β-sheets and the importance of matching surfaces.
abstract: We use molecular dynamics simulations to investigate the water-mediated self-assembly of two amyloidogenic β-sheets of hIAPP(22-27) peptides (NFGAIL). The initial configurations of β-sheet pairs are packed with two different modes, forming a tube-like nanoscale channel and a slab-like 2-D confinement, respectively. For both packing modes, we observe strong water drying transitions occurring in the intersheet region with high occurrence possibilities, suggesting that the "dewetting transition"-induced collapse may play an important role in promoting the amyloid fibrils formation. However, contrary to general dewetting theory prediction, the slab-like confinement (2-D) shows stronger dewetting phenomenon than the tube-like channel (1-D). This unexpected observation is attributed to the different surface roughness caused by different packing modes. Furthermore, we demonstrated the profound influence of internal surface topology of β-sheet pairs on the dewetting phenomenon through an in silico mutagenesis study. The present study highlights the important role of packing modes (i.e., surface roughness) in the assembly process of β-sheets, which improves our understanding toward the molecular mechanism of the amyloid fibrils formation. In addition, our study also suggests a potential route to regulate controllably the self-assembly process of β-sheets through mutations, which may have future applications in nanotechnology and biotechnology.
authors.affiliation: Bio-X Lab, Department of Physics, and Soft Matter Research Center, Zhejiang University, Hangzhou 310027, China.
authors.forename: Zaixing
authors.initials: Z
authors.lastname: Yang
authors.forename: Biyun
authors.initials: B
authors.lastname: Shi
authors.forename: Hangjun
authors.initials: H
authors.lastname: Lu
authors.forename: Peng
authors.initials: P
authors.lastname: Xiu
authors.forename: Ruhong
authors.initials: R
authors.lastname: Zhou
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D044367:Phase Transition; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D012984:Software; D013499:Surface Properties; D014867:Water / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; C478380:amylin (22-27); D014867:Water