An Entropic Fitness? The Specific Adsorption of Proteins Amidst Polymer Brushes

Brenda Rubenstein, Columbia University

Proteins in crowded environs interact fundamentally differently than in vacuo, or even in vitro. Studies have recently demonstrated that in the crowded environs of the cell, proteins not only manifest different solubilities and catalytic activities, but different folding, binding, and self-assembly patterns. These results beg the question: can crowding be used as a tool to manipulate protein behavior?



In this work, we consider how proteins fold and bind amidst polymer brushes. Polymer brushes represent a particularly fascinating form of crowding agent because their ability to exclude volume may be fine-tuned – the properties of a polymer brush grafted onto a surface may be delicately altered by merely changing the brush’s grafting density and/or the individual polymers’ lengths and branching patterns. By simulating our proteins as heteropolymers on a lattice attempting to fold and bind amidst a sea of non-interacting homopolymers, we demonstrate that the free energies of binding may be controllably altered by crowding a substrate with brushes of varying densities and heights. We furthermore show that proteins with different archetypal folding and binding pathways are affected by crowding to varying degrees. Whereas the binding of “Fischer”-type proteins, proteins that fold autonomously in solution, is completely obstructed, natively-disordered proteins possess a comparative resilience to crowding agents. These findings suggest that polymers may not only be used to manipulate protein behavior in the nanomachinery of the future, but that proteins may possess different entropic fitnesses with respect to such polymers in the cell.


 

Abstract Author(s): B.M. Rubenstein (1), I. Coluzza (2), and M.A. Miller (2)<br /><br />(1) Columbia University Department of Chemical Physics<br />(2) Cambridge University Center for Computational Chemistry (CUC3)