Cholesterol alters the phase separation in model membranes containing hBest1
- Human retinal pigment epithelial (RPE) cells express the transmembrane Ca2+-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 (Cs−1) 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 Ca2+ 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 ΔGmixπ values (reduction of phase separation) of hBest1/POPC/Chol films. For the hBest1/SM/Chol monolayers, the negative values of ΔGmixπ are retained and equalized with the values of ΔGmixπ 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.
Author of HS Reutlingen | Andreeva, Tonya |
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URN: | urn:nbn:de:bsz:rt2-opus4-37290 |
DOI: | https://doi.org/10.3390/molecules27134267 |
ISSN: | 1420-3049 |
Erschienen in: | Molecules |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Journal article |
Language: | English |
Publication year: | 2022 |
Tag: | POPC; SM; cholesterol; hBest1; phase separation |
Volume: | 27 |
Page Number: | 12 |
Article Number: | 4267 |
DDC classes: | 540 Chemie |
Open access?: | Ja |
Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |