Interlocking nanomechanics of kinesins and tubulins

Kinesin-microtubule railways transport cargo in cells and are essential for eukaryotic life. The forces generated by these railways originate in the mechanical cycles of their component molecules. The mechanical cycle of tubulin consumes GTP and drives the dynamic instability of microtubules. The mechanical cycle of kinesins consumes ATP and drives them to step directionally along microtubules. We recently discovered that these two mechanical cycles interlock, so that changes in the structure and mechanics of the microtubule can control patterns of kinesin stepping, whilst motile kinesins can control the curvature, stiffness and longevity of microtubules. I propose to illuminate the molecular mechanisms that connect the mechanical cycles of kinesin and tubulin, using protein engineering combined with single molecule mechanics at unprecedented resolution. Defining the mechanisms by which kinesins and tubulins sense, respond to and manipulate each other's mechanics and dynamics will transform our understanding of the machinery of intracellular transport.