Cargo-mediated mechanisms reduce inter-motor mechanical interference, promote load-sharing and enhance processivity in teams of molecular motors

Abstract

In cells, multiple molecular motors work together to carry membranous cargoes including vesicles and organelles along a network of cytoskeletal filaments. The fluidity of the cargo surface has been potentially associated with both positive and negative effects in transport, but the physical mechanisms, at the motor and cargo level that might be responsible, are not clear. To explore these mechanisms, we developed a 3D dynamical simulation of cargo transport along microtubules by teams of canonically non-cooperative kinesin-1 motors that accounts for membrane fluidity by explicitly simulating the Brownian dynamics of motors on the cargo surface. Our results suggest that cargo surface fluidity reduces inter-motor interference and promotes load-sharing thereby decreasing off-rates, allows the adaptive recruitment of motors and a co-operative increase in on-rates resulting from the 3D geometry. These effects altogether result in enhanced cargo run-lengths, most significantly at low ATP concentrations with implications for transport in vivo and artificial cargo design.

The nanocaterpillar's random walk: diffusion with ligand–receptor contacts

“…Going further, other effects that could be studied include the details of binding kinetics, e.g. non-exponential kinetics in DNA hybridization, [77][78][79] which could also impact the long time response; 42 mobility of the leg roots, corresponding to fluidity of the bilayer; 10,80 and out-of-equilibrium effects, such as white blood cells streaming in blood flow, 5,76 active stepping of molecular motors, 49,81,82 or proteins that actively cleave bonds on influenza A. 17,36 Accounting for such effects would require adapting bond dynamics to include increased bond rigidity or bond lifetime in flow; 3,[83][84][85][86][87] binding kinetics coupled to the number of bonds; 47,49 or memory effects associated with dead zones created by cleaved bonds.…”