Molecular dynamics simulations of the human ocular lens with age and cataract
Molecular dynamics simulations of the human ocular lens with age and cataract
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DOI：
10.1016/j.bbamem.2022.184025
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发表时间：
2022-08-17
影响因子：
3.4
通讯作者：
Klauda, Jeffery B.
中科院分区：
文献类型：
--
作者：
Fernandes, Joshua B.;Yu, Yalun;Klauda, Jeffery B.
人眼透镜主要由细长的静态纤维组成，其特征在于高稳定性和低转换，其在组成和性质上与其他生物膜显著不同。胆固醇（Chol）和鞘脂（SL）以高浓度存在，包括饱和SL，如二氢鞘磷脂（DHSM）。过去的分子动力学模拟表明，DHSM和高浓度的Chol的存在下，有助于更高的秩序在脂膜。目前的研究模拟了更复杂的人类透镜膜模型。开发了代表74 +/- 6岁白内障晶状体和22 +/- 4、41 +/- 6和69 +/- 3岁健康晶状体的生理组成的模型。随着年龄的增长，Chol和神经酰胺浓度增加，甘油磷脂浓度降低。白内障时，神经酰胺浓度升高，胆固醇和甘油磷脂浓度降低。每个脂质的表面积，氘序参数（SCD），甾醇倾斜角，电子密度分布，双层厚度，链交错，二维径向分布函数（2D-RDF），脂质聚类，和氢键计算所有的模拟。所有系统均表现出低的表面积/脂质和高双层厚度，表明强垂直包装。SCD参数表明类似的，与饱和的尾巴在疏水性的膜具有升高的顺序的核心。垂直包装和酰基尾顺序增加与年龄和白内障的条件。侧向扩散随着年龄和白内障的增加而减少，2D-RDF分析显示老年和白内障模型的长程结构增加。在未来的工作中，检查膜蛋白的透镜，这些模型可以作为一个生理学上准确的代表性的透镜脂质体。
The human ocular lens consists primarily of elongated, static fibers characterized by high stability and low turnover, which differ dramatically in their composition and properties from other biological membranes. Cholesterol (Chol) and sphingolipids (SL) are present at high concentrations, including saturated SLs, such as dihyrosphingomyelin (DHSM). Past molecular dynamics simulations demonstrated that the presence of DHSM and high Chol concentration contributes to higher order in lipid membranes. This current study simulated more complex models of human lens membranes. Models were developed representing physiological compositions in cataractous lenses aged 74 +/- 6 years and in healthy lenses aged 22 +/- 4, 41 +/- 6, and 69 +/- 3 years. With older age, Chol and ceramide concentrations increase and glycerophospholipid concentration decreases. With cataract, ceramide concentration increases and Chol and glycerophospholipid concentrations decrease. Surface area per lipid, deuterium order parameters (SCD), sterol tilt angle, electron density profiles, bilayer thickness, chain interdigitation, two-dimensional radial distribution functions (2D-RDF), lipid clustering, and hydrogen bonding were calculated for all simulations. All systems exhibited low surface area per lipid and high bilayer thickness, indicative of strong vertical packing. SCD parameters suggest similarly, with saturated tails in the hydrophobic core of the membrane having elevated order. Vertical packing and acyl tail order increased with both age and cataract condition. Lateral diffusion decreased with age and cataracts, with the older and cataractous models demonstrating increased long-range structure by the 2D-RDF analysis. In future work examining the membrane proteins of the lens, these models can serve as a physiologically accurate representation of the lens lipidome.