Inverse Correlation between Amyloid Stiffness and Size

• DOI: 10.1021/jacs.8b10142
• Publication Date: 2018-12-18T18:27:11Z
• Authors: Roy Nassar; Eric Wong; Jörg Gsponer; Guillaume Lamour
• Keywords: Models, Molecular; 0301 basic medicine; polypeptide; Amyloid; Protein Conformation; beta sheet; correlation analysis; amyloid protein; 530; Article; Hydrogen bonds; Stiffness; Protein Aggregates; 03 medical and health sciences; controlled study; protein structure; Global properties; molecular size; Polypeptide chain; Glycoproteins; Mechanical Phenomena; Cross sectional area; hydrogen bond; Packing density; 500; Hydrogen Bonding; molecular mechanics; Mechanical stability; amino acid sequence; Biomechanical Phenomena; [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry; Linear correlation; protein stability; rigidity; Axial stiffness; Inverse correlation; computer analysis; Size dependence; [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph]

We reveal that the axial stiffness of amyloid fibrils is inversely correlated with their cross-sectional area. Because amyloid fibrils' stiffness is determined by hydrogen bond (H-bond) density with a linear correlation, our finding implies that amyloid fibrils with larger radial sizes are generally softer and have lower density H-bond networks. In silico calculations show that the stiffness-size relationship of amyloid fibrils is, indeed, driven by the packing densities of residues and H-bonds. Our results suggest that polypeptide chains which form amyloid fibrils with narrow cross sections can optimize packing densities in the fibrillar core structure, in contrast to those forming wide amyloid fibrils. Consequently, the density of residues and H-bonds that contribute to mechanical stability is higher in amyloid fibrils with narrow cross sections. This size dependence of nanomechanics appears to be a global property of amyloid fibrils, just like the well-known cross-β sheet topology.