Meeting Abstract
Muscle cells generate an entirely new organelle as they differentiate from their stem cell precursors. The structures that emerge from this process are responsible for the production and transmission of force from the molecular to the organismal scale, and for the specialized adaptation of the resulting fibers. The transition from pre-myofibril to developing and mature myofibril is mechanically regulated. The mechanical context, e.g. surrounding tissue stiffness and active forcing of cell edges as surrounding cells contract, partially control the reorganization of the actin/myosin/cross-linker bundles. The ordering of these pre-fibrils is in contrast to similar structures present in other load-bearing or motile cells. Non-muscle stress-fibers contain many or most of the same constituent proteins but never transition to the stable crystalline order seen in developing myofibers. The Allen Institute for Cell Science is producing a high-throughput dataset that explores these transitions as human induced-pluripotent stem cells differentiate into derived-cardiomyocytes. We develop and present a spatial model, parameterized by this high-throughput imaging, that tracks the force and diffusion mediated rearrangement of proteins within a developing myofibril. This model treats each protein as an object with distinct dimensions, stiffnesses, energy-dependent kinetics, and connectivities. Comparison of large-scale runs to structure-organization metrics derived from the Allen Institute for Cell Science’s growing muscle-differentiation image corpus allows us to characterize the emergence of sarcomereic organization.
