Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Av. Universidad s/n, Col. Chamilpa, Cuernavaca, Morelos, 62210, Mexico.
Division of Strategic Research and Development, Graduate School of Science and Engineering, Saitama University, Japan.
Biochim Biophys Acta Biomembr. 2020 Feb 1;1862(2):183101. doi: 10.1016/j.bbamem.2019.183101. Epub 2019 Oct 28.
The effect of cholesterol and ergosterol on supported lipid bilayers composed of 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and egg sphingomyelin (eSM) in a 1/1 M ratio was studied using atomic force microscopy. The addition of ergosterol or cholesterol to these membranes considerably modifies both the structure and the dynamics of the domains present in them. The height of the eSM enriched domains increases with concentration of both sterols, but more markedly with ergosterol. The height of the POPC enriched domains increases with concentration in a similar manner for both sterols. This effect is larger for eSM than for POPC when ergosterol, not cholesterol, is present. Domain coverage increases with both sterols at 5 mol% but decreases at 20 mol% and almost disappears at 40 mol%. The size of the eSM enriched domains decreases with sterol concentration, more markedly with cholesterol. Bilayer rupture forces show that overall stiffness increases with the addition of 5 mol% cholesterol, but only for the eSM enriched domains with ergosterol at the same concentration. At larger sterol concentrations the stiffness of both regions becomes reduced. At 40 mol% sterol concentration, both membranes present the same rupture force value. To gain mechanistic insight into these observations we performed Quantum Mechanical calculations and Molecular Dynamics simulations of the sterol molecules. We found that conformational freedom for the sterol molecules is quite different. This difference might be behind the observed phenomena. Finally, the different action of sterols on membrane properties is related to the sterol-dependent ionophoretic activity of polyene antibiotics.
使用原子力显微镜研究了胆固醇和麦角固醇对 1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱（POPC）和卵鞘磷脂（eSM）以 1/1 M 摩尔比组成的支撑脂质双层的影响。向这些膜中添加麦角固醇或胆固醇会极大地改变存在于其中的结构域的结构和动力学。eSM 富集结构域的高度随两种甾醇的浓度增加而增加，但添加麦角固醇时增加更明显。富含 POPC 的结构域的高度以相似的方式随两种甾醇的浓度增加而增加。当存在麦角固醇而不是胆固醇时，这种效应对于 eSM 比对于 POPC 更大。在 5 mol％时，两种甾醇的域覆盖率均增加，但在 20 mol％时降低，在 40 mol％时几乎消失。eSM 富集结构域的尺寸随甾醇浓度减小，添加胆固醇时更为明显。双层破裂力表明，添加 5 mol％胆固醇会增加整体刚度，但仅在相同浓度的麦角固醇存在时才会增加 eSM 富集结构域的刚度。在较大的甾醇浓度下，两个区域的刚度都会降低。在 40 mol％甾醇浓度下，两种膜均具有相同的破裂力值。为了深入了解这些观察结果，我们对甾醇分子进行了量子力学计算和分子动力学模拟。我们发现，甾醇分子的构象自由度差异很大。这种差异可能是观察到的现象背后的原因。最后，甾醇对膜性质的不同作用与多烯抗生素的甾醇依赖性离子通道活性有关。
