MOLECULAR FORCES INVOLVED IN FORCE GENERATION DURING SKELETAL-MUSCLE CONTRACTION

Recent advances in protein chemistry and the kinetic analysis of tensi on transients in skeletal muscle fibres have enabled us to elucidate t he molecular forces involved in force generation by cross-bridges. On the basis of the temperature effect, we conclude that the elementary s tep that generates force is an endothermic reaction (the enthalpy chan ge Delta H degrees=124 kJ mol(-1) at 15 degrees C), which accompanies a large entropy increase (Delta S degrees= 430 J K-1 mol(-1)) and a re duction in the heat capacity (Delta p=-6.4 kJ K-1 mol(-1)). Thus, it c an be concluded that the force-generating step is an entropy-driven re action. The above results suggest that hydrophobic interactions are th e primary cause of force generation, and that polar interactions (hydr ogen bonding and charge interactions) are involved to a lesser degree. On the basis of the thermodynamic data, we estimate that during force generation approximately 50 nm(2) of surface area is involved for hyd rophobic interactions and another 30 nm(2) for polar interactions. The se data suggest that both the actomyosin interaction and the cleft clo sure of the myosin head are essential for force generation.