Force Effects on Biochemical Kinetics

Force is an important component in the proper functioning of tissues and cells. In processes ranging from the contraction of muscles to the alignment of chromosomes at the metaphase plate, forces must be adjusted to the proper levels by cells. At the molecular level, it is clear that the motor molecules and other enzymes must respond to changes in mechanical forces by altering enzymatic function. Recent technical advances, primarily the atomic force microscope and laser tweezers, enable us to measure forces at the single molecule level to test how force is transduced into a change in enzyme activity. A priori, four basic mechanisms of coupling enzyme rate and force are considered. The mechanisms extend from the cellular to the molecular level. For example, polymer assembly rates and cytoskeletal matrix concentration are potentially modified by force in ways that feed back on critical enzyme rates. In studies of the known mechanosensitive enzymes, myosin and other motors, the bacterial flagellar rotor, and the F0F1 ATPase, the molecular mechanisms used to transduce force changes into activity changes have not been clearly defined, although it is reasonable to speculate about the nature of these mechanisms from the atomic structures and nanometer measurements of movement.