The goal of this research program is to relate the biochemical and mechanical states of the mechanism of muscle contraction by studying the detailed mechanical properties of muscle preparations in which the concentration of relevant chemical species is subject to experimental variation. Force transients, which occur after the length or load on a muscle is rapidly altered and are related to molecular events of the cross-bridge cycle, will be measured in conditions of reduced myofibrillar concentration of the reaction substrate (ATP), at increased concentration of the reaction products (ADP and Pi) and at aletered pH. These conditions can be imposed on """"""""skinned"""""""" single muscle fiber preparations which have had their surface membrane removed. The effects of altered chemical environment on the transient events will be related to the known kinetics of actomyosin in solution to determine how organization of the filament lattice influences rates of intermediate reactions and how free energy change of the chemical reaction is coupled into force generation. The influence of the lateral spacing between the filaments on the mechanical compliance and reaction rates of the cross-bridge will be determined in skinned and intact muscle fibers. A new white light diffraction method, using acousto-optic deflection, will be used to control sarcomere length at the high spacial and time resolution necessary to perform the transient experiment in skinned muscle fibers. A new method of rapid activation of the fibers will be used to improve the uniformity and reproducibility of the contractions. This will involve flash photolysis of a photolabile compound, termed caged ATP, in the interior of rigor muscle fibers in the presence of calcium. The pulse of light will release ATP and initiate the contraction. The significance of these studies extends over a broad range of muscle physiology and cell motility.
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