Fig. 3. The diffusion coefficient (D) is time- and orientation-dependent in muscle. (A) A 3-dimensional schematic of a muscle fiber shows the major barriers to diffusion, where radial diffusion (red arrow) is hindered both by the sarcoplasmic reticulum (blue shading), which is a partial membrane that surrounds myofibrils (small cylinders), and by the thick and thin filament lattice (thin black lines). In contrast, there are comparatively few barriers to axial diffusion (blue arrow), and elements that potentially limit axial diffusion, such as Z-disks (not shown), have little effect on D. Green spheroids represent mitochondria. (B) D of PCr in white muscle of goldfish is reduced from the value in solution (D of PCr in solution is shown at a diffusion time of zero) (Ellington and Kinsey, 1998), and declines to a steady state value that is lower for radial diffusion, due to the presence of intracellular barriers such as the sarcoplasmic reticulum [data from Kinsey et al. (Kinsey et al., 1999) ©1999, John Wiley and Sons, Ltd, reproduced with permission]. (C) Hindered radial diffusion in muscle (red line) increases the time required for PCr to diffuse a given distance compared to diffusion in water (broken black line). RMS is root mean square displacement and reflects the average movement of a molecule. (D) There is a large percent change in the radial diffusion time over the short intracellular diffusion distances that characterize most cells. Therefore, below a threshold diffusion distance of about 8 µm (time-dependent range), shorter diffusion distances can support higher metabolic rates without diffusion limitation.