Many types of muscle grow by increasing cell size, such that in juvenile animals the cells are small, but during development they may become quite large. This leads to changing constraints both on the transport of oxygen and nutrients from the blood to the cell and intracellular metabolite diffusion across the cell. Thus, during development muscle fibers must preserve function while navigating a multi-dimensional energetic landscape that encompasses molecular transport, ATP demand, behavior, body mass range and evolutionary history. This work will address the question: Are muscle cells as big as they can be without compromising function? The P.I.s will examine changes in muscle structure and function during growth in a diversity of fishes and crustaceans. The experimental objectives are: (1) to use light and electron microscopy to characterize cell architecture, (2) to apply magnetic resonance spectroscopy to in vivo and ex vivo muscle preparations to determine rates of ATP turnover, (3) to construct a reaction-diffusion mathematical model that integrates oxygen flux and intracellular metabolite diffusive flux, and (4) to use the model to define the limits of metabolic function for any combination of fiber size and ATP turnover. It is expected that muscle cells approach molecular transport limitation as the animals grow, but that all stages of development will be influenced by limits that are ultimately encountered only in the adults. This is a collaborative research project with a variety of broader impacts. A primary emphasis will be on the training of undergraduate and graduate students, including underrepresented groups. This training will be implicitly cross-disciplinary, and will involve both engineering and biology students. These students will be involved in experimental approaches that include the use of state-of-the-art magnetic resonance instruments at the National High Magnetic Field Laboratory, as well as rigorous mathematical modeling and computer programming.
