Tuning ensemble-averaged cargo run length via fractional change in mean kinesin number

The number of motors carrying cargos in biological cells is not well-defined, instead varying from cargo to cargo about a statistical mean. Predictive understanding of motility in cells therefore requires quantitative insights into mixed ensembles of cargos. Toward this goal, here we employed Monte Carlo simulations to investigate statistical ensembles of cargos carried by a Poisson-distributed number of motors. Focusing on the key microtubule-based motor kinesin-1, our simulations utilized experimentally determined single-kinesin characteristics and alterations in kinesin's on- and off-rates caused by cellular factors and/or physical load. We found that a fractional increase in mean kinesin number enhances the ensemble-averaged cargo run length and amplifies run-length sensitivity to changes in single-kinesin on-rate and off-rate. These tuning effects can be further enhanced as solution viscosity increases over the range reported for cells. Together, our data indicate that the physiological range of kinesin number sensitively tunes the motility of mixed cargo populations. These effects have rich implications for quantitative and predictive understanding of cellular motility and its regulation.