Vesicular exocytosis of neurotransmitters is a key process in neuronal communication. This release is “quantal”, i.e., all vesicles release similar amounts of neurotransmitters (e.g. serotonin). How does the cell know which vesicle is exocytosis-ready? We hypothesize that intra-vesicular serotonin affects the membrane mechanical properties (i.e. ‘lipid bilayer order’) in a concentration-dependent manner, which in turn affects the probability of exocytosis. Atomic Force Microscopy measurements on artificial lipid bilayers show that the vesicular membrane composition is just right for it to respond to physiological serotonin concentrations. We also probe this in live serotonergic cells. We employ three-photon microscopy to measure serotonin concentration inside individual vesicles in a label-free manner and perform simultaneous single-photon spectral imaging of a membrane marker dye to measure lipid order. We find that vesicles with higher serotonin concentrations have lower membrane order and higher exocytosis probability. Therefore, membrane mechanics allows intra-vesicular serotonin to control its own exocytosis.
Sudipta Maiti is Professor and Chair of the Department of Chemical Sciences at the Tata Institute of Fundamental Research (TIFR). Sudipta majored in Physics at IIT Kanpur, obtained a Ph.D. in Biophysics from the University of Pennsylvania, and was a post-doctoral fellow at Cornell University, before joining TIFR. His current research interest spans several areas of Biophysics, namely, protein aggregation, monoaminergic neurotransmission, membrane interactions, and the development of optical techniques for studying biological phenomena.
