Tension-based regulation mechanism explaining the coordinated stepping of kinesin-1 along the microtubule. This model proposes that thermodynamically favorable transitions between a head’s conformational states (semi-open to open, and open to closed) are regulated by entropy loss due to neck linker stretching in dimeric kinesin. The semi-open, open, and closed conformational states of the head are indicated in orange, blue, and red, respectively, with the α6 helix, which connects to the neck linker, highlighted as a rod. The neck linker is shown in green, while the α4 helix, which directly interacts with the microtubule, and the neck coiled-coil are in yellow. Premature binding of the tethered semi-open head to the microtubule in the ATP-waiting state is prevented by an intolerable increase in neck linker tension, as it causes substantial entropy reduction (red rectangle). This contrasts with a monomeric head with a disordered neck linker, where the semi-open-to-open transition is thermodynamically favorable (right). Even after ATP-induced isomerization of the microtubule-bound head, increasing tension prohibits rebinding of the tethered head to the rear binding site (green hexagonal box), enabling preferential binding to the forward site. In the two-head–bound state, the trailing and leading heads stabilize in closed and open conformations, respectively, explaining why the trailing head hydrolyzes ATP and detaches from the microtubule before the leading head (purple rectangle).