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

Abstract

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.

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

“…Tryptophan [376][377][378], Glycine [139,284], Glutamate [139], Aginine [379], Alanine [379], 5-aminolevulinic acid and its esters [380], L-dopa [138,199,381,382] Nucleotides ATP [383], UMP [384], DNA [385], ADOMET [381] Sugars and carbohydrates Trehalose [386], Gastrodin [387], Mannitol [199], 1,3,7-trimethyluric acid [388] Neurotransmitters Dopamine [138,[389][390][391][392][393][394][395][396][397], Serotonin [138,378,389,396,[398][399][400][401][402], Adenosine [138], Melatonin [138,229,378,389,[403][404]…”

Understanding of the interaction of biological macromolecules with lipids using vibrational sum‐frequency generation spectroscopy

“…[61] Several groups have used the C-H stretch of the lipids to characterize the local conformation as well as the ordering of the hydrocarbon chain of the lipids at the interface in the presence of different molecules as well as different conditions. [46][47][48][49][50][51][52][53][56][57][58][59][60][61][62] For example, Bonn et al have utilized the C-H stretch of the hydrocarbon chain of lipids to understand the effect of cholesterol on the packing of the lipids at different surface pressure. [58] Similarly, several other groups have utilized the C-H stretch of the hydrocarbon chain of lipids to understand the conformational change of lipid and interaction with neurotransmitter, DNA, and other biomolecules.…”

“…[58] Similarly, several other groups have utilized the C-H stretch of the hydrocarbon chain of lipids to understand the conformational change of lipid and interaction with neurotransmitter, DNA, and other biomolecules. [47][48][49][50][51][52][53]62] The interfacial water near to the different head groups of lipid has been characterized by the VSFG technique. Conventional VSFG measurements show that the intensity of the VSFG signal of the O-H stretch of water enhances in the presence of the lipids compared with the air/water interface and the enhancement of the water signal is higher at the charged lipids compared with the zwitterionic (Figure 2A).…”

“…Conventional VSFG measurements show that the intensity of the VSFG signal of the O-H stretch of water enhances in the presence of the lipids compared with the air/water interface and the enhancement of the water signal is higher at the charged lipids compared with the zwitterionic (Figure 2A). [11,12,50,63] It has been concluded that the presence of phospholipids monolayer causes an increase in the orientation of water molecules in the interfacial region. The increase in intensity of the OH signal of water is attributed to the static electric field established at the interface by the charged head group of lipid molecules.…”

“…VSFG technique has the capability to understand the molecular behavior at the interface, and hence, it has been also implemented at the model membrane interfaces (consisting of lipid monolayer at air/water interface) to understand the structure of lipid and interfacial water molecules during the complex biological processes. [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] In this review, we have focused on the discussion of the structural change of lipid and interfacial water molecules during the fibrillation of proteins, interaction with hydrated proton, and neurotransmitter interaction related to synaptic vesicles.…”