When: Monday, 16th June (2014), 12:00h
Place: Departamento de Física Teórica de la Materia Condensada, Facultad Ciencias, Módulo 5, Aula de Seminarios (5ª Planta).
Speaker: Erkan Tuzel, Assistant Professor of Physics, Biomedical Engineering and Computer Science Department of Physics, Worcester Polytechnic Institute.
Intracellular cargo transport frequently involves multiple motor types, either having opposite directionality or having the same directionality but different speeds. Although significant progress has been made in characterizing kinesin motors at the single-molecule level, predicting their ensemble behavior is challenging and requires tight coupling between experiments and modeling to uncover the underlying motor behavior. To understand how diverse kinesins attached to the same cargo coordinate their movement, we carried out microtubule gliding assays using pairwise mixtures of motors from the kinesin-1, 2, 3, 5 and 7 families. A coarse-grained computational model of gliding assays was developed and found to recapitulate the experiments. Simulations incorporated published force-dependent velocities and run lengths, along with mechanical interactions between motors bound to the same microtubule. The simulations show that the force-dependence of detachment is the key parameter that determines gliding speed in multi-motor assays, while motor compliance, surface density and stall force all play minimal roles. Simulations also provide estimates for force-dependent dissociation rates suggesting that kinesin-1 and the mitotic motors kinesin-5 and -7 maintain microtubule association against loads, while kinesin-2 and -3 readily detach. This work uncovers unexpected motor behavior in multi-motor ensembles and clarifies functional differences between kinesins that carry out distinct mechanical tasks in cells.