Effect of hydrophobic residues on amyloid formation under steady shear and at interfaces

Abstract

A surprisingly large number of proteins of different shapes, sizes, and functions are capable of undergoing fibrillization transformations in which protein monomers become unstable and begin to combine in a crystalline fashion to form long, thin structures, known as amyloid fibrils. Accumulation of amyloid fibrils leads to a number of disorders, including Alzheimer’s and Parkinson’s diseases. Shearing flows and hydrophobic interfaces are ubiquitous throughout the body and known to contribute strongly to fibrillization, yet the influence of these forces on amyloid formation are not well understood. Previous investigations regarding the effect of agitation on fibrillization kinetics have failed to reach a consensus on whether the effect is due to a simple increase in mixing, alterations of protein structure caused by shear extensional forces, or a combination of shear and hydrophobic interfaces.