This research will apply a recently developed, ultrasensitive interferometric imaging technique to map, onto images of a living cell, the distribution of motion of its macromolecules. The larger macromolecules can behave as optical markers even though they may be spaced too closely to be optically resolved, and interference between their scatterings of coherent incident light contains statistically rich information about their relative disposition. This information can be extracted by quantitative, pixel-by-pixel analysis of the map intensities, and quantitative measures of the scales of length and time over which their motions are correlated can be established even when the spatial scale proves to be fine in comparison to an optical wavelength. Finally, the structure and composition of skeletal muscle are such that the force generators (crossbridges) themselves are its dominant Rayleigh scatterers. Interferometric Rayleigh maps of intact skeletal muscle fibers developing steady tension are thus likely to yield information that has an intimate and unusually direct connection with the scale on which one of the Life Processes is organized. This research represents a potentially major technical advance in our ability to observe macromolecular movements in the living cell. The technique, once perfected, can probably be adapted to other problems of regular movement at the macromolecular level, also.
