Restructuring of Membrane Water and Phospholipids in Direct Interaction of Neurotransmitters with Model Membranes Associated with Synaptic Signaling: Interface-Selective Vibrational Sum Frequency Generation Study.

Comprehensive molecular-level understanding of the role of interfacial water and phospholipids associated with synaptic membranes during their direct interaction with neurotransmitters is essential because of their involvement in synaptic signaling. Herein, the interfacial regions of the synaptic membranes mimicking anionic and zwitterionic phospholipids are probed in the presence of dopamine and serotonin neurotransmitters using surface-specific vibrational sum frequency generation technique. Neurotransmitters intrude into the headgroup region of both zwitterionic and anionic lipids by restructuring the interfacial water associated with the phospholipids, although the restructuring mechanism is different for both lipids. Neurotransmitters also decrease the overall ordering of both the phospholipids probably by creating gauche defects. Neurotransmitters restructure the surface water, conformation, and the ordering of the hydrocarbon chains of the zwitterionic and anionic phospholipids associated with synaptic membranes, which could be potentially an important step for synaptic signaling.