Movement of myosin VI monomer-coated nanospheres on extracted keratocyte actin networks assessed from the experiment and simulation. (a) A schematic of the simplified model used. (a, left) Four monomers are coupled through the nanospheres, all bound to the actin filaments (the myosin VI flexibility is depicted as a spring and the centroid of the nanosphere is shown as a yellow circle). (a, middle) The monomer on the right releases from actin upon binding to ATP and searches for the next binding site. (a, right) The monomer binds at random to an actin filament, and then strokes (curved arrow). The stroke causes a distension of all monomers (depicted as distension of connecting springs) along with movement of the centroid (depicted by movement of the yellow circle). The extent of movement is determined by the balance of force between the four connected monomers. (b) Simulated end–end speed for limited (1 nm), moderate (3 nm), and very large (50 nm) distensions permitted. (c) Simulated trajectories of monomer-coated nanosphere motion for moderate distensions. (d) Experimental trajectories of myosin VI monomer-coated nanospheres moving along an extracted keratocyte. (e) Sample trajectories from panel d aligned such that the cell periphery is at the top and the cell center is at the bottom. All movement, without exception, is toward the cell center. (f) Comparison of end–end speeds from the experiment (blue) and simulation (red). (g) Comparison of frame–frame speeds between the experiment (blue) and simulation (red). Bars, 1 µm.