Transport model of chemical secretion process for tracking exocytotic event dynamics using electroanalysis

A unified model is developed to analyze the key features of the chemical secretion process observed in experimental studies of various vesicles with application to electroanalytical measurements of vesicular exocytosis. The intimately coupled dynamics and kinetics are simultaneously resolved based on continuum fluid flow, mass transport, and linear elasticity theories combined with biomembrane mechanics. We report three case studies of exocytosis, including a large electroporated granule of the mast cell, a small and clear synaptic vesicle, and a medium size vesicle in the chromaffin cell. The simulation results for each case are compared with electroanalytical measurements from the literature. The results provide a theoretical ground for defining the rate-controlling step(s) of an exocytotic sequence, allowing interpretation of electroanalysis data. Thus, it provides a tool for theoretical verification of competing hypotheses of what controls/limits messenger release during exocytosis. Simulations show that the pore size, the pore opening velocity, and the swelling dynamics of the granule matrix play the key roles in controlling the messenger release kinetics.