Twisting and untwisting of actin and tropomyosin filaments may be involved in the molecular mechanism of muscle contraction

Abstract

Polarized fluorescence microscopy in “ghost” muscle fibers containing F-actin, tropomyosin, and myosin heads labeled with FITC-phalloidin, 5-IAF, and 1,5-IAEDANS probes, respectively, provided new insights into the molecular mechanisms of muscle contraction. Simulation of different stages of muscle contraction revealed significant changes in probe orientation and mobility, as well as variations in the bending stiffness of actin and tropomyosin filaments. Fluorescence analysis showed that in the AM∗•ATP state, myosin heads deviate from the axis of actin and weakly interact with thin filaments. Actin filaments exhibit excessive twisting, while tropomyosin filaments untwist. This is accompanied by a 115 % increase in actin filament stiffness and a 32 % increase in tropomyosin filament stiffness. The transition to the AM•ADP state aligns the myosin heads and induces actin untwisting. The release of inorganic phosphate reduces actin stiffness by 45 % and increases tropomyosin stiffness by 9 %. We propose that the untwisting of supertwisted actin filaments, combined with myosin head tilting towards actin and increased tropomyosin twist and stiffness, causes thin filaments to slide along thick filaments. The synchronized sliding of thin filaments relative to thick filaments ultimately generates the mechanical force that drives muscle contraction.