FIGURE 4.

Much of the biasing mechanism is assumed to occur in the parked geometry of frame 5 in Fig. 2, where the external load acting on the microtubule-bound head leads to long dwell times (see Waiting Mechanism). However, the free head could have, in the time before ATP uptake, an opportunity to bind rearward during a period when forward binding is virtually excluded (due to no zippering). Thus, bias would then be [ATP] dependent due to [ATP] dependence of the waiting mechanism. In panel a, a fast step is outlined that corrects this undesired backward stepping. Since the forward head experiences strain due to the rearward-bound head, ATP uptake is greatly inhibited in the forward head, and thus, there exists a much larger probability that the rearward head detaches first (at the expense of one ATP hydrolysis). In contrast, panel b outlines how a “real” backward step may occur once the waiting mechanism has ended, i.e., once ATP has bound to the microtubule-bound head. Notice that if the rearward head binds as in panel b, the forward head is at least one chemical step ahead of the rearward head. With a few assumptions, the forward head in panel b may then be expected to release first on average. Events in panel b where instead the rearward head unbinds will alter the simple relation between binding and stepping direction, but these (potentially uncommon) events are ignored at the level of detail in this article.