A Mechanochemical Mechanism for Muscle Contraction

Abstract

A mechanism for contraction in skeletal muscle is proposed in which the tension-generating site is located within the core of the thick (myosin) filament, specifically within the trypsin-sensitive hinge region of the myosin rod. The force-developing mechanism is thought to be the transfer of energy from ATP splitting in the globular head of one molecule directly to the hinge region of an adjoining molecule, resulting in a phase transition from crystalline to amorphous within the hinge segment of the second molecule. Binding of MgATP at the actinmyosin interface is considered to be a release mechanism. The model leads to out-of-phase oscillating movement of the cross bridges.In recent years, a large body of literature has accumulated demonstrating that the concept of "melting" during shrinkage and crystallization when polymeric systems are stretched can be regarded as a first-order phase transition, and that dimensional changes in fibrous proteins are intimately related to changes in crystallinity (1,2). A striking illustration of this phenomenon is seen, for example, in the case of a collagen fiber which may undergo abrupt contraction at a characteristic temperature, under a constant small load, to approximately l/6 of its normal, low-temperature length. The transition occurs over a temperature interval of only 2-30C. As is now well documented, the sharpness of the phase transition in the fibril is a macroscopic manifestation of the collagen helix --coil cooperative transformation. The equilibrium between crystalline and amorphous states, as a function of stress on the fiber, follows classical thermodynamic relations (between force, length, and temperature) in which the crystalamorphous phase transition is coupled with dimensional changes. Flory (3) has provided a detailed analysis of the dimensional and force changes to be expected on crystallization of linear polymeric systems and has proposed that a phase transition from an oriented, crystalline to a random, amorphous state underlies muscular contraction. A similar suggestion was put forward by Pryor (4).Consider a length of polymer chain that consists of ordered and disordered segments in which the end points are fixed in space. If the ordered (crystalline) segments are melted, the increased number of conformational states resulting from the increased number of rotatable bonds tends to contract the chain. Since the chain ends are fixed, a force that stems from a rise in conformational entropy of the chain will be generated. rhus, orientation imposed by stretching should promote crystallization, and, conversely, crystallization in a previously oriented polymer should diminish the stress. Although the equilibrium between crystalline and amorphous regions o0 the chain can be displaced with temperature, it is well known that protonation of charged side groups or binding of a charged solute of low molecular weight can also promote a shift in the force-elongation relations as a function of the composition of the external solution. Several authors (3-9) hav...

The descending limb of the force‐sarcomere length relation of the frog revisited.

“…The same dependence is expected by the S-2 based phase transition model (Harrington, 1971). And it is also predicted by a thick-filament shortening model G.…”

“…For example, the first row of cross-bridges facing the bare-zone might be non-functional (Harrington, 1971), or filament lengths might be slightly different from those assumed. There is some uncertainty as to the exact length of the filaments.…”

Fluorescence resonance energy transfer measurements of distances in actin and myosin. A critical evaluation

“…They may in fact be too small to detect. Harrington (1971) suggested an entirely different molecular mechanism for the interaction of myosin with F-actin. He proposed that a large-scale 'melting' occurs inthe peptide joining the $1 to the rod portion of the myosin molecule.…”

Smooth muscle myosin: regulation and properties

“…Thus such phosphorylation-induced changes in myosin were observed in studies using cryo-atomic force microscopy to image thiophosphorylated and non-thiophosphorylated smooth muscle myosin molecules. A significant shortening was observed in the hinge region at the juncture of subfragment 2 and light meromyosin (figure 4), thought to reflect a helix-coil transition (Zhang et al 1997), as has been proposed for skeletal muscle myosin under different conditions (Harrington 1971). The tail length of skeletal myosin has also been shown to decrease by 22 nm over a 17 C increase in temperature (Walker et al 1991).…”