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胆固醇改变了含有 hBest1 的模型膜的相分离。

Cholesterol Alters the Phase Separation in Model Membranes Containing hBest1.

机构信息

Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tzankov Str., 1164 Sofia, Bulgaria.

Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, 1113 Sofia, Bulgaria.

出版信息

Molecules. 2022 Jul 2;27(13):4267. doi: 10.3390/molecules27134267.

DOI:10.3390/molecules27134267
PMID:35807512
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9268032/
Abstract

Human retinal pigment epithelial (RPE) cells express the transmembrane Ca-dependent Cl channel bestrophin-1 (hBest1) of the plasma membrane. Mutations in the hBest1 protein are associated with the development of distinct pathological conditions known as bestrophinopathies. The interactions between hBest1 and plasma membrane lipids (cholesterol (Chol), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and sphingomyelin (SM)) determine its lateral organization and surface dynamics, i.e., their miscibility or phase separation. Using the surface pressure/mean molecular area (π/A) isotherms, hysteresis and compressibility moduli (C) of hBest1/POPC/Chol and hBest1/SM/Chol composite Langmuir monolayers, we established that the films are in an LE (liquid-expanded) or LE-LC (liquid-condensed) state, the components are well-mixed and the Ca ions have a condensing effect on the surface molecular organization. Cholesterol causes a decrease in the elasticity of both films and a decrease in the ΔG values (reduction of phase separation) of hBest1/POPC/Chol films. For the hBest1/SM/Chol monolayers, the negative values of ΔG are retained and equalized with the values of ΔG in the hBest1/POPC/Chol films. Shifts in phase separation/miscibility by cholesterol can lead to changes in the structure and localization of hBest1 in the lipid rafts and its channel functions.

摘要

人视网膜色素上皮 (RPE) 细胞表达质膜上的跨膜 Ca 依赖性 Cl 通道蛋白 bestrophin-1（hBest1）。hBest1 蛋白的突变与被称为 bestrophinopathies 的不同病理状况的发展有关。hBest1 与质膜脂质（胆固醇 (Chol)、1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸胆碱 (POPC) 和鞘磷脂 (SM)) 之间的相互作用决定了其侧向组织和表面动力学，即它们的混溶性或相分离。使用表面压力/平均分子面积 (π/A) 等温线、滞后和压缩模量 (C)，我们研究了 hBest1/POPC/Chol 和 hBest1/SM/Chol 复合 Langmuir 单层膜的 hBest1/POPC/Chol 和 hBest1/SM/Chol 复合 Langmuir 单层膜，我们确定这些膜处于 LE（液体膨胀）或 LE-LC（液体冷凝）状态，各组分混合良好，Ca 离子对表面分子组织具有凝聚作用。胆固醇会降低两种膜的弹性，并降低 hBest1/POPC/Chol 膜的ΔG 值（相分离减少）。对于 hBest1/SM/Chol 单层膜，仍保留ΔG 的负值，并与 hBest1/POPC/Chol 膜中的ΔG 值相等。胆固醇引起的相分离/混溶性的变化可能导致 hBest1 在脂质筏中的结构和定位及其通道功能发生变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/aaa8f45262f1/molecules-27-04267-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/3b8db0fc8341/molecules-27-04267-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/35f156cc65cf/molecules-27-04267-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/d4f13a01ecf8/molecules-27-04267-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/b664989c8186/molecules-27-04267-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/2dfe876d40e8/molecules-27-04267-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/f6745bec0d83/molecules-27-04267-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/aaa8f45262f1/molecules-27-04267-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/3b8db0fc8341/molecules-27-04267-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/35f156cc65cf/molecules-27-04267-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/d4f13a01ecf8/molecules-27-04267-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/b664989c8186/molecules-27-04267-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/2dfe876d40e8/molecules-27-04267-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/f6745bec0d83/molecules-27-04267-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9581/9268032/aaa8f45262f1/molecules-27-04267-g007.jpg

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本文引用的文献

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Adv Colloid Interface Sci. 2022 Apr;302:102619. doi: 10.1016/j.cis.2022.102619. Epub 2022 Feb 22.
2
How Does Liquid-Liquid Phase Separation in Model Membranes Reflect Cell Membrane Heterogeneity?模型膜中的液-液相分离如何反映细胞膜的异质性？
Membranes (Basel). 2021 Apr 28;11(5):323. doi: 10.3390/membranes11050323.
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Condensing Effect of Cholesterol on hBest1/POPC and hBest1/SM Langmuir Monolayers.
胆固醇对hBest1/POPC和hBest1/SM朗缪尔单分子层的凝聚作用。
Membranes (Basel). 2021 Jan 13;11(1):52. doi: 10.3390/membranes11010052.
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Miscibility of hBest1 and sphingomyelin in surface films - A prerequisite for interaction with membrane domains.hBest1 与神经鞘磷脂在表面膜中的混溶性 - 与膜域相互作用的前提条件。
Colloids Surf B Biointerfaces. 2020 May;189:110893. doi: 10.1016/j.colsurfb.2020.110893. Epub 2020 Feb 21.
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Effects of Concentration and Surface Pressure on MBP Interaction with Cholesterol in Langmuir Films.浓度和表面压力对朗缪尔膜中髓鞘碱性蛋白与胆固醇相互作用的影响。
Scanning. 2017 Nov 7;2017:1542156. doi: 10.1155/2017/1542156. eCollection 2017.
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