Mesoscale stochastic modeling and simulations of exocytosis of bioparticles*

Exocytosis is a highly regulated mechanism utilized by cells to release secretory vesicles and drug bioparticles to the membrane surface. After the initial fusion of the vesicle with the plasma membrane, the post-fusion pore opening is critical for the successful drug release. Despite its important role in exocytosis, the mechanism of vesicle merging with membrane is still poorly understood. Recent evidence shows the active involvement of actin coating and remodeling in regulating the dynamics of the pore opening. The mode of the vesicle merging, either fully opening, stalled or kiss-and-run is determined by the physical parameters of the membrane, the vesicle and the actin filaments. In this work, we develop and implement a stochastic model to systematically study the process of exocytic pore opening in mesoscopic scale. The model takes the actin recruitment into account and is based on the Monte Carlo simulations. Using our model we explore the effects of plasma membrane surface tension, bioparticle size and actin coating generated force. Our results are consistent with some experimental measurements, and may provide guidelines for transcellular drug delivery design.