An Equilibrium Model for the Combined Effect of Macromolecular Crowding and Surface Adsorption on the Formation of Linear Protein Fibrils

Abstract

The formation of linear protein fibrils has been previously shown to be enhanced by volume exclusion or crowding in the presence of a high concentration of chemically inert protein or polymer, and by adsorption to membrane surfaces. An equilibrium mesoscopic model for the combined effect of both crowding and adsorption upon the fibrillation of a dilute tracer protein is presented. The model exhibits behavior that differs qualitatively from that observed in the presence of crowding or adsorption alone. The model predicts that in a crowded solution, there exist critical values of the volume fraction of crowder or intrinsic energy of tracer-surface interaction about which the tracer protein undergoes an extremely cooperative transition - approaching a step function - between existing almost entirely as a slightly self-associated species in solution and existing almost entirely as a highly self-associated and adsorbed species.