ADP release can explain spatially-dependent kinesin binding times.

Cytoskeletal-motor assemblies self-organize to achieve cellular functions ranging from delivering intracellular cargoes to generating forces in mitosis. Advancements in single-molecule experiments have revealed immense detail about motor detachment and stepping, but relatively little regarding the attachment process. With newly available spatially parameterized motor binding times from an optical trap, the evaluation of mechanistic models for binding becomes possible. We find that a model limited by both diffusive search and ADP-release best explains the data. The coupled chemo-mechanical nature of this interaction is more malleable than either separately, possibly explaining the rich diversity and regulation observed in cells. More broadly, our study provides a timely vignette on leveraging computations with experiments to understand how geometry and other complexities shape protein-protein interactions.