Departamento de Física, Centro de Investigación y de Estudios Avanzados, Av. IPN No. 2508, México, DF, 07360, Mexico; Tecnológico Nacional de México, Campus Zacatecas Occidente, Ave. Tecnológico No. 2000, Col. Loma la Perla, Sombrerete, Zacatecas, 99102, Mexico.
Departamento de Física, Centro de Investigación y de Estudios Avanzados, Av. IPN No. 2508, México, DF, 07360, Mexico.
Biophys Chem. 2020 Feb;257:106275. doi: 10.1016/j.bpc.2019.106275. Epub 2019 Oct 24.
We performed molecular dynamics simulations of a lipid bilayer consisting of POPC and cholesterol at temperatures from 283 to 308K and cholesterol concentrations from 0 to 50% mol/mol. The purpose of this study was to look for the existence of structural differences in the region delimited by these parameters and, in particular, in a region where coexistence of liquid disordered and liquid ordered phases has been proposed. Our interest in this range of concentration and temperature responds to the fact that polyene ionophore activity varies considerably along it. Two force fields, CHARMM36 and Slipids, were compared in order to determine the most suitable. Both force fields predict non-monotonic behaviors consistent with the existence of phase transitions. We found the presence of lateral structural heterogeneity, statistical in nature, in some of the bilayers occurring in this range of temperatures and sterol concentrations. This heterogeneity was produced by correlated ordering of the POPC tails and not due to cholesterol enrichment, and lasts for tens of nanoseconds. We relate these observations to the action of polyenes in these membranes.
我们在温度为 283 至 308K 和胆固醇浓度为 0 至 50%摩尔/摩尔的条件下，对由 POPC 和胆固醇组成的脂质双层进行了分子动力学模拟。本研究的目的是寻找这些参数限定的区域内是否存在结构差异，特别是在已经提出存在液态无序相与液态有序相共存的区域内。我们对该浓度和温度范围感兴趣是因为聚烯类离子载体的活性在该范围内有很大的变化。为了确定最合适的力场，我们比较了 CHARMM36 和 Slipids 两种力场。这两种力场都预测了非单调行为，这与相变的存在一致。我们发现，在温度和甾醇浓度的这个范围内，一些双层存在横向结构异质性，这是一种统计性质。这种非均质性是由 POPC 尾部的相关有序化产生的，而不是由于胆固醇富集，并且持续数十纳秒。我们将这些观察结果与聚烯类在这些膜中的作用联系起来。
