Leekumjorn Sukit, Sum Amadeu K
Virginia Polytechnic Institute and State University, Department of Chemical Engineering, Blacksburg, VA 24061, USA.
Biochim Biophys Acta. 2006 Nov;1758(11):1751-8. doi: 10.1016/j.bbamem.2006.06.010. Epub 2006 Jun 14.
As a way to quantify the diffusion process of molecular compounds through biological membranes, we investigated in this study the dynamics of DMSO through an 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) bilayer system. To properly account for the diffusion of DMSO due to a concentration gradient, a double DPPC bilayer was setup for our simulations. In such configuration, the aqueous phases can be explicitly associated with the extra and intracellular domains of the membrane, which is seldom the case in studies of single lipid bilayer due to the periodicity imposed by the simulations. DMSO molecules were initially contained in one of the aqueous phases (extracellular region) at a concentration of 5 wt.%. Molecular dynamics simulation was performed in this system for 95 ns at 350 K and 1 bar. The simulations showed that although many DMSO molecules penetrated the lipid bilayer, only about 10% of them crossed the bilayer to reach the other aqueous phase corresponding to the intracellular region of the membrane. The simulation time considered was insufficient to reach equilibrium of the DMSO concentration between the aqueous phases. However, the simulations provided sufficient information to estimate parameters to apply Fick's Law to model the diffusion process of the system. Using this model, we predicted that for the time considered in our simulation, the concentration of DMSO in the intracellular domain should have been about half of the actual value obtained. The model also predicted that equilibrium of the DMSO concentration in the system would be reached after about 2000 ns, approximately 20 times longer than the performed simulation.
作为量化分子化合物通过生物膜扩散过程的一种方法，我们在本研究中研究了二甲基亚砜（DMSO）通过1,2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）双层系统的动力学。为了恰当地考虑由于浓度梯度导致的DMSO扩散，我们为模拟设置了双层DPPC。在这种配置下，水相可以明确地与膜的细胞外和细胞内区域相关联，而在单脂质双层的研究中由于模拟所施加的周期性，这种情况很少见。DMSO分子最初以5 wt.%的浓度包含在其中一个水相（细胞外区域）中。在该系统中于350 K和1 bar下进行了95 ns的分子动力学模拟。模拟结果表明，尽管许多DMSO分子穿透了脂质双层，但只有约10%的分子穿过双层到达对应于膜细胞内区域的另一水相。所考虑的模拟时间不足以使水相之间的DMSO浓度达到平衡。然而，模拟提供了足够的信息来估计参数，以便应用菲克定律来模拟系统的扩散过程。使用该模型，我们预测在我们模拟所考虑的时间内，细胞内区域中DMSO的浓度应该约为所获得实际值的一半。该模型还预测系统中DMSO浓度的平衡将在约2000 ns后达到，大约比所进行的模拟长20倍。
