Ivanova Nikoleta, Chamati Hassan
Department of Physical Chemistry, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria.
Institute of Solid State Physics, Bulgarian Academy of Sciences, Tzarigradsko Chaussée 72, 1784 Sofia, Bulgaria.
ACS Omega. 2025 May 6;10(19):19235-19242. doi: 10.1021/acsomega.5c01375. eCollection 2025 May 20.
The major components of cell membranes are phospholipids. Due to their amphiphilic structure, in a solution they arrange in bilayers. The phase behavior of lipid bilayers and thus their functions, such as cellular organization, cellular transport, membrane fusion, drug delivery, and others, are susceptible to temperature changes and/or admixing with biologically active materials. A typical representative of phospholipids is SOPC (1-stearoyl-2-oleoyl--glycero-3-phosphocholine) possessing a saturated hydrocarbon acyl chain and an unsaturated one, exhibiting a single cis double bond. Cholesterol plays a primordial role in maintaining the mechanical stability of the cell membrane. We present a comprehensive review of the phase behavior of the binary mixture of SOPC with cholesterol as a function of the temperature explored via atomistic molecular dynamics and Slipids force field in the vicinity of the experimental melting point, = 279 K, corresponding to the temperature driven phase transition from the gel phase (L) to the liquid disordered phase (L). The behavior of the thermodynamic properties and structural characteristics with different concentrations of cholesterol show that the pure SOPC bilayer and its counterpart mixed with 10 mol % cholesterol exhibit phase transitions at 277 and 276 K, respectively, and that cholesterol reinforces the fluidity of the bilayer leading to the emergence of a liquid ordered phase (L). At cholesterol contents larger than 30 mol %, the bilayer exhibits a liquid ordered phase (L) at any temperature. The ensuing phase diagram is found to reproduce reasonably well its counterpart constructed experimentally.
细胞膜的主要成分是磷脂。由于其两亲结构，在溶液中它们排列成双层。脂质双层的相行为及其功能，如细胞组织、细胞运输、膜融合、药物递送等，易受温度变化和/或与生物活性物质混合的影响。磷脂的一个典型代表是1-硬脂酰-2-油酰基-sn-甘油-3-磷酸胆碱（SOPC），它具有一条饱和烃酰基链和一条不饱和烃酰基链，呈现出一个单一的顺式双键。胆固醇在维持细胞膜的机械稳定性方面起着至关重要的作用。我们通过原子分子动力学和Slipids力场，在实验熔点（(T_m) = 279 K）附近，对SOPC与胆固醇的二元混合物的相行为随温度的变化进行了全面综述，该温度对应于从凝胶相（L）到液体无序相（L）的温度驱动相变。不同胆固醇浓度下的热力学性质和结构特征表明，纯SOPC双层及其与10 mol%胆固醇混合的对应物分别在277 K和276 K发生相变，并且胆固醇增强了双层的流动性，导致出现液体有序相（L）。当胆固醇含量大于30 mol%时，双层在任何温度下都呈现出液体有序相（L）。结果发现，由此得到的相图与通过实验构建的相图相当吻合。
