Richard Bayford

Biological systems are often exposed to mechanical perturbations, which may modulate many biochemical processes. Ligand binding involves a wide range of structural changes in the receptor protein, from hinge movement of entire domains to minor sidechain rearrangements in the binding pocket residues. Hydrophobic ligand binding to protein alters the system’s vibrational free energy, allowing different conformational states of allosteric proteins. Excess hydrophobicity in protein–ligand binding generates mechanical force along the peptide backbone through the hydrophobic effect. We describe mechanically strained peptide structures involved in protein aggregation to determine the transition between the initial condensation of hydrophobic polypeptide chains into ordered fibrillar structures. This transition is due to the excess attractive hydrophobic force by ligand binding within proteins into fibrillar assemblies. The process of fibrillar formation has a mechanosensitive nature, which significantly influences the pathogenesis of several neurodegenerative diseases.