Diffusion and redistribution of lipid-like molecules between membranes in virus-cell and cell-cell fusion systems

The kinetics of redistribution of lipid-like molecules between the membranes of two fused spherical vesicles is studied by solving the time-dependent diffusion equation of the system. The effects on the probe redistribution rate of pore size at the fusion junction and the relative sizes of the vesicles are examined. It is found that the redistribution rate constant decreases significantly, but not drastically, as the relative size of the pore to that of the vesicles decreases (the bottleneck effect). In general, the time scale of the probe redistribution rate is determined by the size of the vesicles that is loaded with the probe before the activation of the fusion. For a pore size 50 A in diameter and a typical diffusion coefficient of 10(-8) cm2/s for lipids, the mixing half times for typical virus-cell and cell-cell fusion systems are less than 30 ms and above 200 s, respectively. Thus, although the redistribution of lipid-like probes by diffusion is not rate limiting in virus-cell fusion, redistribution by diffusion is close to rate limiting in spike-protein mediated cell-cell fusion.