DHA 分子对模型细胞膜物理性质影响的分子观点,Journal of Chemical Information and Modeling

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DHA 分子对模型细胞膜物理性质影响的分子观点
Journal of Chemical Information and Modeling ( IF 5.6 ) Pub Date : 2022-05-05 , DOI: 10.1021/acs.jcim.2c00074
Xiu Li ₁ , Shiying Zhou ₁ , Xubo Lin ₁

Affiliation

二十二碳六烯酸 (DHA) 是一种 ω-3 多不饱和脂肪酸，可被细胞摄取，对正常的神经元和视网膜功能至关重要。然而，DHA 分子对质膜的详细物理影响仍不清楚。因此，在这项工作中，我们进行了微秒级粗粒度分子动力学（MD）模拟，以揭示 DHA 分子与模型细胞膜之间的相互作用。众所周知，细胞膜可以分为液体有序（L _o）和液体无序（L _d) 由于脂质和蛋白质之间的不同相互作用而导致的膜结构域。为了捕捉这一特征，我们采用了三组分相分离脂质膜，并在当前工作中同时考虑了阴离子和中性 DHA 分子。我们的研究结果表明，DHA 分子可以自发地自组装成纳米团簇，与脂质膜融合，并优选定位于L _d膜结构域。在膜融合过程中，DHA分子可以改变脂质膜的内在跨膜电位，阴离子DHA分子的作用更为显着。此外，DHA 分子主要存在于L _d膜结构域基本上以浓度依赖性方式调节脂质链顺序、膜厚度、胆固醇偏好和胆固醇触发器的差异，从而进一步促进叶内动力学的稳定性并抑制叶间动力学（或促进膜结构域）注册）膜域。简而言之，我们工作中揭示的 DHA 分子对模型细胞膜物理性质的影响在分子水平上将为理解 DHA 分子的生物学功能提供有用的见解。

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Molecular View on the Impact of DHA Molecules on the Physical Properties of a Model Cell Membrane

Docosahexaenoic acid (DHA) is a ω-3 polyunsaturated fatty acid, which can be uptaken by cells and is essential for proper neuronal and retinal function. However, the detailed physical impact of DHA molecules on the plasma membrane is still unclear. Hence, in this work, we carried out μs-scale coarse-grained molecular dynamics (MD) simulations to reveal the interactions between DHA molecules and a model cell membrane. As is known, the cell membrane can segregate into liquid-ordered (L_o) and liquid-disordered (L_d) membrane domains due to the differential interactions between lipids and proteins. In order to capture this feature, we adopted the three-component phase-separated lipid membranes and considered both anionic and neutral DHA molecules in the current work. Our results showed that DHA molecules can spontaneously self-assemble into nanoclusters, fuse with lipid membranes, and localize preferably in L_d membrane domains. During the membrane fusion process, DHA molecules can change the intrinsic transmembrane potential of the lipid membrane, and the effects of anionic DHA molecules are much more significant. Besides, the presence of DHA molecules mainly in the L_d membrane domains could regulate the differences in the lipid chain order, membrane thickness, cholesterol preference, and cholesterol flip-flop basically in a concentration-dependent manner, which further promote the stability of the intraleaflet dynamics and inhibit the interleaflet dynamics (or promote membrane domain registration) of the membrane domains. In short, the impact of DHA molecules on the physical properties of a model cell membrane on the molecular level revealed in our work will provide useful insights for understanding the biological functions of DHA molecules.

更新日期：2022-05-05

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