Cryoprotective mechanism of using Ficoll for cell cryopreservation at non-cryogenic temperatures: A molecular dynamics study
Cryoprotective mechanism of using Ficoll for cell cryopreservation at non-cryogenic temperatures: A molecular dynamics study
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DOI：
10.1016/j.ijheatmasstransfer.2018.06.142
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发表时间：
2018-12-01
影响因子：
5.2
通讯作者：
Zhang，Yuwen
中科院分区：
文献类型：
--
作者：
Mao，Yijin;Han，Xu;Zhang，Yuwen
采用分子动力学模拟研究了Ficoll（一种高度致密的球形多糖）作为非渗透性冷冻保护剂在高于- 80 °C的温度下进行细胞冷冻保存的机制。分别制备了三种类型的模拟箱，分别模拟了ficoll -二甲基亚砜(DMSO)-水、蔗糖-DMSO-水和DMSO-水体系，并以液体模拟优化电位（OPLS-all）作为分子体系的势函数进行了描述。每一种情况下的整个分子体系首先被完全平衡到已知浓度、密度和温度的状态，与相应的现有或新测量的相图一致。随后，通过计算原子位置的径向密度分布（RDF）和均方根距离（RMSD），进行了分子动力学模拟，以表征液态水分子在每个分子系统中心预先放置的冰核周围的行为。结果表明，在不同的非低温温度（−10 °C,−20.3 °C,−33.9 °C和−80 °C）下，含有Ficoll分子的体系表现与其他两种体系有显著差异。Ficoll分子明显阻止了水分子靠近冰核，同时降低了水分子的活度。这些结果与之前的热研究结果一致，这些研究表明，使用Ficoll可以最大限度地减少此类溶液的再结晶，并且还在分子水平上提供了定性解释，为什么Ficoll有助于在非低温下长期储存细胞。
Molecular dynamics simulations were carried out to investigate the cryoprotective mechanism of using Ficoll, a highly compact spherical polysucrose, as a non-permeating cryoprotectant for practices of cell cryopreservation at temperatures higher than −80 °C. Three types of simulation boxes were prepared for Ficoll-dimethyl sulfoxide (DMSO)-water, sucrose-DMSO-water, and DMSO-water systems, respectively, and depicted with the Optimized Potentials for Liquid Simulations (OPLS-all) as potential function for molecular systems. The entire molecular system for each scenario was firstly fully equilibrated into a state with known concentration, density and temperature, in agreement with the corresponding existing or newly measured phase-diagrams. Thereafter, molecular dynamics simulations were performed to characterize the behavior of liquid water molecules surrounding a pre-sited ice nucleus that was placed at the center of each molecular system by calculating the radial density distribution (RDF) and root-mean-square distance (RMSD) of atomic positions. The results showed that the system with Ficoll molecules present behaved significantly different from the other two systems at various non-cryogenic temperatures (−10 °C, −20.3 °C, −33.9 °C, and −80 °C). The Ficoll molecules obviously prevent the water molecules from approaching the ice nuclei, and simultaneously lower the activities of the water molecules. These results agree well with previous thermal studies that demonstrate the effect of using Ficoll to minimize recrystallization of such solutions, and also provide a qualitative explanation on a molecular level for why Ficoll facilitates long-term storage of cells at non-cryogenic temperatures.