Figure 7. Internal or External Strain Facilitates Kinesin Stepping(A) Model for ATP-dependent kinesin stepping by neck linker–generated strain. ATP binding to the front head causes neck linker docking, which increases intramolecular strain (red arrow); forward strain on the rear head favors its dissociation after it transits to a weakly bound ADP state (panel D). After its dissociation, the head shifts forward, biasing its attachment to the next available forward binding site. Note, however, that intramolecular strain from the stretched neck linkers (Figure S1) may suffice to release the rear head in its ADP state, without neck linker docking.(B) Strain on kinesin heads can be generated by external load (black arrows). Forward load increases the strain on the rear head by pulling the neck linker. This favors the rear head detachment and displacement toward the microtubule plus end (right). Similarly, a backward load pulls the front head backward as a result of strain-dependent detachment (left). This type of stepping can occur in the absence of ATP and the neck linker.