A mechanical model demonstrates that the orientation of myosin head levers during the working stroke follows a uniform distribution in isometrically stimulated muscle fibers.
Geometric cross-bridge model aids sarcomere simulations; leaves open validation in cardiac muscle systems.
A myosin II head is modelled during the working stroke (WS) by three rigid segments articulated between them: the motor domain (S1a), the lever (S1b) and the rod (S2). Hypothesis 4 introduced in accompanying Paper 2 states that the lever of a WS head moves in a fixed plane where the position of S1b is characterized by the angle θ. This assumption allows the geometrization of a cross-bridge, i.e. the poly-articulated chain consisting of five rigid segments: the actin filament (Afil), S1a, S1b, S2, and the myosin filament (Mfil). The equations established in Paper 2 are operative to calculate the number of heads potentially in WS for a Mfil surrounded by six Afil. In addition, the value of the angles θ of the levers belonging to these WS heads is accessible. This census leads to an integer number (N p ) of angular positions (θi) distributed discretely between θ up and θ down , the two values that delimit θ during the WS. The number of Mfil per half-sarcomere (hs) is estimated between 400 and 2000 depending on the typology, figures that induce Gaussian variability for each of the N p values θi calculated for a single Mfil. By summing the Gaussian N p densities and after normalization, we obtain a probability density (d G ) of the continuous variable θ between θ up and θ down . The function d G is calculated for a random length of a hs between 1 and 1.1 μm where the binding rate of the myosin heads is maximum. From this reference length, the hs is shortened 11 times with a step of 1 nm, i.e. a total of 11 nm. For each shortening, a count of the new θi positions is performed, which leads to a new probability density d G . The classic statistical law that approximates these 12 distributions of θ is the Uniform law between θ up and θ down . Other conditions and values given to the data of the algorithmic procedure lead to a similar result, hence the formulation of hypothesis 5: the distribution of the angle θ follows an identical uniform law in all the hs of a muscle fiber stimulated in isometric conditions.
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Sylvain Louvet (2019) studied this question.
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