Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, Indiana.
Department of Physics, Carnegie Mellon University, Pittsburgh, Pennsylvania.
Biophys J. 2023 Mar 21;122(6):1118-1129. doi: 10.1016/j.bpj.2023.02.016. Epub 2023 Feb 17.
Dopamine (DA) is a neurotransmitter that also acts as a neuromodulator, with both functions being essential to brain function. Here, we present the first experimental measurement of DA location in lipid bilayers using x-ray diffuse scattering, solid-state deuterium NMR, and electron paramagnetic resonance. We find that the association of DA with lipid headgroups as seen in electron density profiles leads to an increase of intermembrane repulsion most likely due to electrostatic charging. DA location in the lipid headgroup region also leads to an increase of the cross-sectional area per lipid without affecting the bending rigidity significantly. The order parameters measured by solid-state deuterium NMR decrease in the presence of DA for the acyl chains of PC and PS lipids, consistent with an increase in the area per lipid due to DA. Most importantly, these results support the hypothesis that three-dimensional diffusion of DA to target membranes could be followed by relatively more efficient two-dimensional diffusion to receptors within those membranes.
多巴胺（DA）是一种神经递质，也作为神经调质发挥作用，这两种功能对大脑功能都至关重要。在这里，我们首次使用 X 射线漫散射、固态氘 NMR 和电子顺磁共振实验测量了 DA 在脂质双层中的位置。我们发现，正如电子密度分布中所见，DA 与脂质头部基团的结合导致了膜间斥力的增加，这很可能是由于静电充电引起的。DA 在脂质头部基团区域的位置也会导致每个脂质的横截面积增加，而不会显著影响弯曲刚度。固态氘 NMR 测量的有序参数在存在 DA 的情况下，对于 PC 和 PS 脂质的酰基链会降低，这与由于 DA 导致的每个脂质的面积增加一致。最重要的是，这些结果支持了这样一种假设，即 DA 向靶膜的三维扩散可能随后是在这些膜内的受体上进行相对更有效的二维扩散。
