Microtubules are cytoskeletal filaments that provide tracks for molecular motor proteins and establish physical connections between distant parts of the cell. Recent work has shown that the microtubule lattice possesses remarkable structural plasticity, with its conformation modulated by the binding of MAPs and motors. Motor-induced changes can be detected microns away by other MAPs and motors, implying that the lattice adapts to binding interactions. However, the way in which microtubule plasticity responds to mechanical forces remains poorly understood. In particular, the magnitude of mechanically induced changes of the microtubule lattice, and their impact on the binding interface and thus on the affinity of MAPs and motors at the single-molecule level, is not well understood. In this study, we developed experimental assays to apply tensile forces on single microtubules using optical tweezers combined with high-contrast fluorescence microscopy. Decorating the microtubules with quantum dots enabled us to measure, with nanometer precision, mechanical distortions of ∼0.4% across the lattice under tensile forces ranging from 7 to 16 pN—comparable to the forces generated by one or two kinesin-1 motors, respectively. Furthermore, we found that under similar force changes (0-17 pN), the average binding rate of the kinesin-1 KIF5B isoform decreased by ∼20%, while its average dissociation rate increased by ∼10%, resulting in a reduced average run length. In extreme cases, run length was reduced by as much as 46% under applied tension. By contrast, no statistically significant effects were observed for the binding or unbinding rates of the KIF5C isoform at the same range of forces. Together, these experiments provide novel insights into the ability of microtubules to act as sensors and transducers of mechanical and biochemical cues across the cell body.
Lurz et al. (Sun,) studied this question.