Multiscale model predictions of X-ray diffraction patterns from nonuniformly stretched actin filaments

In order to explain time-resolved X-ray diffraction data from striated muscle we explored the feasibility of using dynamic 3D models of muscle contraction to predict X-ray diffraction patterns. This approach differs radically from previous attempts, which merely aimed to provide a “best fit” structure for defined quasi-static states, by providing a tool to generate families of structures that evolve in time that explains both the structural (X-ray) and the mechanical data simultaneously. Specifically, we exploit the computational platform MUSICO (Muscle Simulation Code), which was developed originally to model muscle mechanics data, by extending this framework to simulate X-ray diffraction patterns using 3D multiscale models. The platform is conceived primarily as a hypothesis-testing tool in which model predictions are tested against the best available mechanical and X-ray diffraction data on the same system. Our preliminary simulations provided dynamic X-ray diffraction patterns during force development and relaxation in skeletal muscle. The simulated patterns generally predicted well the changes in repetitive molecular spacings and were otherwise similar to the experimental data. Once fully developed, this tool will enable extraction of maximum information from the X-ray patterns, in combination with the physiological data, and therefore provide a template to test hypotheses concerning crossbridge and regulatory protein action in working muscle. Our approach can be extended to any muscle system, and it could ultimately provide an interpretive framework for studying the mechanisms of inherited or acquired diseases.