Seminario BIFI

Vesicular transport is a major cellular activity in eukaryotic cells, responsible for internalization of proteins and their traffic between specific membrane-enclosed compartments. Molecular sorting constitutes the first stage of vesicular transport, whereby specific proteins on lipid membranes are concentrated and distilled into nanometric lipid vesicles. In this talk I will introduce the process of molecular sorting and I will discuss a simple physical picture to explain its overall features. To this purpose, I will formulate a minimal stochastic lattice-gas model that couples spontaneous molecular aggregation with vesicle nucleation, describing the diffusion of molecules on a lipid membrane towards multiple sorting centers that grow due to molecule absorption and are extracted when they reach a sufficiently large size. The efficiency of the distillation process will be measured in terms of the mean time that the molecules spend on the membrane, or mean residence time: a shorter mean residence time would correspond to reduced protein recycling time and faster response to stimuli. The mean residence time will be estimated using a heuristic law from fluid dynamics, which states that the amount of a fluid in a control volume is the product of the fluid influx and the mean residence time of the particles of the fluid. Somehow paradoxically, the efficiency of the molecular sorting process will result to be optimal for intermediate aggregation rates, where sorting centers are few and well separated and the process obeys simple scaling laws. I will compare the predictions of the theory with experimental observations, showing that quantitative measures of endocytic sorting performed in primary endothelial cells are compatible with the hypothesis that this optimal condition is realized in living cells. I will conclude the talk mentioning that the heuristic law for the mean residence time can be rigorously proven for stochastic lattice-gas models under mild assumptions that make the particles distinguishable, so that their residence time can be unambiguously defined. Such assumptions are satisfied by the stochastic lattice-gas model for molecular sorting.