Parallel path mechanisms lead to nonmonotonic force-velocity curves and an optimum load for molecular motor function

Upasana L. Mallimadugula, Eric A. Galburt

Research output: Contribution to journalArticlepeer-review


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 varied, but are almost always considered in the context of a single kinetic pathway that describes motor stepping. However, the multidimensional nature of protein energy landscapes suggests the possibility of multiple reaction pathways connecting two states. Here we investigate the properties of a hypothetical molecular motor able to utilize parallel 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 negative differential conductance. More specifically, regimes exist where increasing opposing force leads to increased velocity and an optimum load 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. Last, 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.

Original languageEnglish
Article number034405
JournalPhysical Review E - Statistical, Nonlinear, and Soft Matter Physics
Issue number3
StatePublished - Mar 2022


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