A Fluorescence Lifetime Imaging Microscopy Supported Investigation on Temperature-Dependent Penetration of Dopamine in a 1,2-Ditetradecanoyl-sn-glycero-3-phospho-(1′-rac-glycerol) Lipid Bilayer

Abstract

Distribution of dopamine, an essential neurotransmitter in mammalian central and peripheral nervous systems, in a lipid bilayer and at the surface of 1,2-ditetradecanoyl-sn-glycero-3-phospho-(1'-rac-glycerol) vesicles has been studied herein. To track the progress of dopamine through different regions of the lipid vesicle, these were synthesized using 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-labeled phospholipid molecules tagged to either the headgroup (NBDPE) or the acyl chain (NBDPG). Dopamine-induced quenching of NBD fluorescence in the lipid vesicles demonstrates that dopamine has a preference to diffuse into the lipid bilayer. The change in the excited state lifetime obtained for NBDPG clearly indicates the preference in dopamine binding. The propositions were supported by fluorescence lifetime imaging microscopy.

A Perspective: Active Role of Lipids in Neurotransmitter Dynamics

“…The subsequent simulations with an alternative molecular mechanics force field methodology (OPLS vs. CHARMM) provided similar observations [42,53]. These theoretical studies indicating strong dopamine-membrane association were further validated by calorimetric [62], nuclear magnetic resonance spectroscopy [63], and fluorescence microscopy [64] experiments.…”

“…Reproduced with the permission from ref. [64]. Copyright 2017 the American Chemical Association membrane surface to the water phase in both simulations and experiments [42,79].…”

“…Various simulation studies [42,54,60,61] and biophysical experiments [51][52][53][54][62][63][64][65][66][67] corroborate this mechanistic division; however, there are notable exceptions to the rule when focusing on the available receptor protein structures and possible MLCs.…”

“…Endocannabinoids such as anandamide, which are derived directly from fatty acids and act as retrograde transmitters [50], deep membrane penetration, and lipid-like dynamics, are to be expected, but the level of membrane permeation or adherence is less evident for the conventional NTs. In fact, several computational and experimental studies have provided solid evidence on the effects of specific NT-lipid interactions and, moreover, highlighted the potential importance of membrane lipid composition (MLC) imbalances for neurological diseases [42,48,[51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67].…”

“…The atomistic MD simulations [42,54,60,61] (Fig. 3a, b) and experiments [51][52][53][54][55][56][62][63][64][65][66][67][68] alike show that the lipid assortment indeed affects NT dynamics profoundly. Majority of the non-peptidic NTs are attracted towards the anionic membrane models to a varying degree [42,56,59,62].…”