(314e) Reaction-Diffusion Processes In Intracellular Muscle Organization and Metabolic Control

An understanding of the factors that control intracellular muscle tissue metabolic and structural organization is important to develop gene therapy strategies to directly treat disease and to develop tissue and metabolic engineering approaches for muscle regeneration.  Muscle from a wide spectrum of animals provides key insight into the factors that control the design of muscles, and knowledge of such design principles may assist in engineering new muscle.  Our work focuses on the analysis of muscle energy metabolism and its relationships to intracellular muscle organization. Our analysis of chemical reaction and diffusion processes in muscle has shown that muscles generally operate under chemical reaction control.  While some muscles operate well within the reaction control domain, and this may constitute a safety factor to allow for higher muscle activity without diffusion limitations, some muscles operate near the transition region between reaction control and diffusion control.  Clearly cells have evolved to stay out of the diffusion control regime.  Through analysis of mitochondrial spatial distribution and lifecycle dynamics we have found that under conditions of oxygen limitation, mitochondria cluster near the capillary oxygen supply, and this reorganization may bring some cells, particularly large muscle cells, into the reaction control regime from an otherwise diffusion control situation; providing further evidence of processes that cause muscle cells to function under reaction control.  Further, we have found that the phosphagen kinase reaction and the myoglobin binding of oxygen do not enhance diffusion in such a way as to lead to reaction control over a broad range of muscle function; these systems play facilitated diffusion roles only in the relatively sharp transition region where diffusion control becomes important. We seek to show in this presentation, through both modeling and comparison to experimental measurements of living tissue, how the application of quantitative bioengineering analysis of chemical reaction and diffusion can provide insight into muscle design and function.