A Parallel Ratchet-Stroke Mechanism Leads to an Optimum Force for Molecular Motor Function.

Abstract

Molecular motors convert chemical potential energy into mechanical work and perform a great number of critical biological functions. Examples include the polymerization and manipulation of nucleic acids, the generation of cellular motility and contractility, the formation and maintenance of cell shape, and the transport of materials within cells. The mechanisms underlying these molecular machines are routinely divided into two categories: Brownian ratchet and power stroke. While a ratchet uses chemical energy to bias thermally activated motion, a stroke depends on a direct coupling between chemical events and motion. However, the multi-dimensional nature of protein energy landscapes allows for the possibility of multiple reaction paths connecting two states. Here, we investigate the properties of a hypothetical molecular motor able to utilize parallel ratchet and stroke translocation mechanisms. We explore motor velocity and force-dependence as a function of the energy landscape of each path and reveal the potential for such a mechanism to result in an optimum force for motor function. We explore how the presence of this optimum depends on the rates of the individual paths and show that the distribution of stepping times characterized by the randomness parameter may be used to test for parallel path mechanisms. Lastly, we caution that experimental data consisting solely of measurements of velocity as a function of ATP concentration and force cannot be used to eliminate the possibility of such a parallel path mechanism. SIGNIFICANCEMolecular motors perform various mechanical functions in cells allowing them to move, replicate and perform various housekeeping functions required for life. Biophysical studies often aim to determine the molecular mechanism by which these motors convert chemical energy to mechanical work by fitting experimental data with kinetic models that fall into one of two classes: Brownian ratchets or power strokes. However, nothing a priori requires that a motor function via a single mechanism. Here, we consider a theoretical construct where a motor has access to both class of mechanism in parallel. Combining stochastic simulations and analytical solutions we describe unique signatures of such a mechanism that could be observed experimentally. We also show that absence of these signatures does not formally eliminate the existence of such a parallel mechanism. These findings expand our theoretical understanding of the potential motor behaviors with which to interpret experimental results.