Continuum and Molecular Modeling of Synaptic Vesicle Docking and Fusion
Transmission of neural information starts by the fusion of a synaptic vesicle inside a neuron with the membrane of the neuron. This fusion process mainly consists of two steps. First one is docking which is to bring the vesicle into the proximity of neuron membrane, against the repulsive forces from electrostatics and hydration. The forces necessary to overcome this repulsion are provided by a family of proteins known as SNARE. Second step is fusion pore formation, which leads to the release of the neurotransmitter, for its collection by the next neuron. We have studied the process of synaptic vesicle fusion using Continuum and CG molecular models. Continuum models of the vesicle and neuron membrane are used to understand the deformation and forces in the membrane system in response to the SNARE and repulsive forces. In another study, a CG-model of SNARE is combined with continuum model of the membranes to analyze the deformation and forces during docking. Our calculations show that about 4-7 SNARE complexes are needed to "dock" the vesicle. Using a continuum model, we estimated the docking time of a synaptic vesicle under the effect of hydrodynamics. We found out that it is the nature of the force generated by the docking machinery which governs it. We have also developed a CG model incorporating lipid bilayer membrane and SNARE complexes to better understand the dynamics of the fusion process.
Coarse Grained Molecular Dynamics (CGMD); Continuum mechanics; Lipid bilayer membrane; SNARE proteins; Synaptic vesicle fusion; Mechanical engineering; Biomechanics; Hydrodynamics; Biophysics
Jenkins, James Thomas; Clancy, Paulette; Jagota, Anand
Ph. D., Mechanical Engineering
Doctor of Philosophy
dissertation or thesis