Investigating the Effect of Cargo-Motor Linkage Stiffness on Cellular Functions of Myosin VI

We examine the effect of cargo-motor linkage stiffness on the mechanobiological properties of the molecular motor Myosin VI. We use the programmability of DNA nanostructures to systematically modulate cargo-motor linkage stiffness and combine it with high precision optical trapping measurements to measure the effect of linkage stiffness on motile properties of Myosin VI. Our single molecule experiments reveal that a stiff cargo-motor linkage leads to shorter step sizes and load-induced anchoring of Myosin VI, while a flexible linkage results in longer steps with frequent detachments from the actin filament under load. These findings suggest a novel regulatory mechanism for tuning the dual cellular roles of anchor and transporter ascribed to Myosin VI [1]. We further make an attempt to investigate the physical basis of our findings using simulations and thermodynamics principles.

[1] Shrivastava, R., Rai, A., Salapaka, M., & Sivaramakrishnan, S. (2019). Stiffness of cargo-motor linkage tunes Myosin VI motility and response to load. Biochemistry