Theoretical analysis of cargo transport by catch bonded motors in optical trapping assays

TL;DR

This paper uses theory and simulations to analyze how catch bonding in dynein motors affects cargo transport in optical trapping assays, revealing complex behaviors like non-monotonic first passage times and detachment forces.

Contribution

It provides a theoretical framework and simulation results that elucidate the impact of catch bonding on cargo transport dynamics, including collective effects in multi-motor systems.

Findings

Catch bonding increases persistent cargo motion.

Non-monotonic behavior of first passage times observed.

Emergent collective effects cause re-entrant phenomena.

Abstract

Dynein motors exhibit catch bonding, where the unbinding rate of the motors from microtubule filaments decreases with increasing opposing load. The implications of this catch bond on the transport properties of dynein-driven cargo are yet to be fully understood. In this context, optical trapping assays constitute an important means of accurately measuring the forces generated by molecular motor proteins. We investigate, using theory and stochastic simulations, the transport properties of cargo transported by catch bonded dynein molecular motors - both singly and in teams - in a harmonic potential, which mimics the variable force experienced by cargo in an optical trap. We estimate the biologically relevant measures of first passage time - the time during which the cargo remains bound to the microtubule and detachment force -the force at which the cargo unbinds from the microtubule, using both two-dimensional and one-dimensional force balance frameworks. Our results suggest that even for cargo transported by a single motor, catch bonding may play a role depending on the force scale which marks the onset of the catch bond. By comparing with experimental measurements on single dynein-driven transport, we estimate realistic bounds of this catch bond force scale. Generically, catch bonding results in increased persistent motion, and can also generate non-monotonic behaviour of first passage times. For cargo transported by multiple motors, emergent collective effects due to catch bonding can result in non-trivial re-entrant phenomena wherein average first passage times and detachment forces exhibit non-monotonic behaviour as a function of the stall force and the motor velocity.