A mathematical understanding of how cytoplasmic dynein walks on microtubules

Cytoplasmic dynein 1 is a dimeric motor protein that walks and transports intracellular cargos towards the minus end of microtubules. In this article we formulate, based on physical principles, a mechanical model to describe the stepping behaviour of cytoplasmic dynein walking on microtubules from the cell membrane towards the nucleus. Unlike previous studies on physical models of this nature, we base our formulation on the whole structure of cytoplasmic dynein 1 to include the temporal dynamics of the individual subunits such as the cargo (for example an endosome, vesicle or bead), two rings of six ATPase domains associated with diverse cellular activities (AAA+ rings) and the microtubule binding domains which allow dynein to bind to microtubules. This mathematical framework allows us to examine experimental observations on dynein across a wide range of different species, as well as being able to make predictions on the temporal behaviour of the individual components of dynein not cur...