Department of Physics, Brock University, St. Catharines, Ontario L2S 3A1, Canada and Institute of Molecular Biosciences, University of Graz, Graz, Austria.
The Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee, Knoxville, Tennessee 37996, USA and Joint Institute for Biological Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA and Biology and Soft Matter Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA.
Soft Matter. 2016 Nov 28;12(47):9417-9428. doi: 10.1039/c6sm01777k.
Cholesterol is an essential biomolecule of animal cell membranes, and an important precursor for the biosynthesis of certain hormones and vitamins. It is also thought to play a key role in cell signaling processes associated with functional plasma membrane microdomains (domains enriched in cholesterol), commonly referred to as rafts. In all of these diverse biological phenomena, the transverse location of cholesterol in the membrane is almost certainly an important structural feature. Using a combination of neutron scattering and solid-state H NMR, we have determined the location and orientation of cholesterol in phosphatidylcholine (PC) model membranes having fatty acids of different lengths and degrees of unsaturation. The data establish that cholesterol reorients rapidly about the bilayer normal in all the membranes studied, but is tilted and forced to span the bilayer midplane in the very thin bilayers. The possibility that cholesterol lies flat in the middle of bilayers, including those made from PC lipids containing polyunsaturated fatty acids (PUFAs), is ruled out. These results support the notion that hydrophobic thickness is the primary determinant of cholesterol's location in membranes.
胆固醇是动物细胞膜的重要生物分子，也是某些激素和维生素生物合成的重要前体。它还被认为在与功能质膜微区（富含胆固醇的区域）相关的细胞信号转导过程中发挥关键作用，通常称为筏。在所有这些不同的生物学现象中，胆固醇在膜中的横向位置几乎肯定是一个重要的结构特征。我们使用中子散射和固态 H NMR 的组合，确定了在具有不同长度和不饱和程度的脂肪酸的磷脂酰胆碱 (PC) 模型膜中胆固醇的位置和取向。这些数据表明，在所有研究的膜中，胆固醇都能快速绕双层法线重新定向，但在非常薄的双层中，胆固醇会倾斜并被迫跨越双层中间平面。胆固醇位于双层中间，包括由含有多不饱和脂肪酸 (PUFA) 的 PC 脂质组成的双层，这种可能性被排除。这些结果支持了这样一种观点，即疏水性厚度是胆固醇在膜中位置的主要决定因素。
