Enhanced Diffusion and Chemotaxis of Catalytically Active Enzymes

Enzymes have been recently proposed to have mechanical activity associated with their chemical activity. In a number of recent studies, it has been reported that enzymes undergo enhanced diffusion in the presence of their corresponding substrate, when this substrate is uniformly distributed in solution. Moreover, if the concentration of the substrate is non-uniform, enzymes and other small molecules have been reported to show chemotaxis---biased stochastic movement in the direction of the substrate gradient---typically towards higher concentrations of this substrate, with a few exceptions. The underlying physical mechanisms responsible for enhanced diffusion and chemotaxis at the nanoscale, however, are still not well understood. We will review the available experimental observations of both enhanced diffusion and chemotaxis, and discuss critically the different theories that have been proposed to explain the two. We put particular emphasis on an equilibrium model recently introduced by us, which describes how the diffusion of dumbbell-like modular enzymes can be enhanced in the presence of substrate, thanks to a binding-induced reduction of the internal fluctuations of the enzyme. We then turn to chemotaxis, beginning with an overview of the chemotaxis-like diffusiophoretic behavior of micron-sized colloids in solute gradients, followed by a discussion of why chemotaxis at the nanoscale requires special consideration. Next, we review the experimental evidence of nanoscale chemotaxis, and describe a number of shortcomings and pitfalls in the phenomenological models for chemotaxis introduced in some of those works. Finally, we discuss a microscopic model for chemotaxis including both non-specific interactions and binding between enzyme and substrate recently developed by us, which overcomes many of these shortcomings, and is consistent with the experimental observations of chemotaxis.