Implications of Quantal Motor Action in Biological Systems
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We demonstrate in this paper that quantal behavior is a central feature of biological motile and contractile systems. Step-like behavior has been demonstrated in the interaction between single molecules and filaments both in the kinesin—microtubule system and in the myosin—actin filament system. We show here that the step-like molecular features appear also in the single intact sarcomere. We studied single sarcomeres of single bumblebee myofibrils, both in the unactivated and activated states. Myofibril-length changes induced by a motor-imposed ramp were accompanied by corresponding sarcomere-length changes. However, the sarcomere-length changes were stepwise. Computer analysis of the stepwise shortening patterns revealed a step-size distribution containing multiple peaks. In the activated state, the peaks were separated by 2.7 nm per half-sarcomere which is the linear actin-subunit spacing. Thus, translation steps are an integer multiple of the actin-subunit spacing. This result parallels the one observed in the kinesin-tubulin spacing, where step size is a multiple of the tubulin-subunit spacing. In the muscle system, however, the steps are preserved on a macroscopic scale, implying high synchrony. The quantal steps are easily explained by a model in which the actin filament propels itself over stationary cross-bridges: if actin binds to the cross-bridges between steps, then the observed quantal result is inevitable.
As probes of contractile phenomena approach the molecular level, the discrete unitary events underlying contraction begin to emerge. Thus, step-like behavior is observed as the single kinesin molecule translates along the microtubule1–4, as the single myosin molecule translates over the actin filament5, and as the single isolated titin molecule is stretched6,7.
What is surprising in all three systems is that the discrete behavior in evidence at the molecular level remains detectable at higher levels of organization. Thus, cilia bend in steps8,9 that are presumably related to stepwise movements along constituent microtubules. And intact sarcomeres shorten in steps10,11 arising either from titin-filament steps or single actomyosin-interaction steps, depending on whether the sarcomere is unactivated or activated. Whereas molecular-scale steps are all but inevitable, steps at higher levels of organization imply an unexpected degree of cooperativity.
In this paper the focus is primarily on steps in the muscle system. We review recent findings of molecular-scale steps. We then consider steps at the single myofibril level as well as older work that reports steps at still higher levels of organization. Why this counterintuitive result is obtained is an issue that will be discussed, and several mechanistic options to mediate the required synchrony will be considered. Finally, I will draw some conclusions about what all of these findings imply about the mechanism of contraction.
KeywordsActin Filament Thin Filament Integer Multiple Sarcomere Length Thick Filament
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