Institute for Computational Science and Technology, SBI Building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City, Vietnam.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Phys Chem Chem Phys. 2022 Mar 9;24(10):6225-6237. doi: 10.1039/d1cp04836h.
Recent studies indicate that there are mechanical differences between normal cells and cancer cells. Because the cell membrane takes part in a variety of vital processes, we test the hypothesis of whether or not two fundamental alterations in the cell membrane, , the overexpression of phosphatidylserine lipids in the outer leaflet and a reduction in cholesterol concentration, could cause the softening in cancer cells. Adopting ten models of normal and cancer cell membranes, we carry out 1 μs all-atom molecular dynamics simulations to compare the structural properties and elasticity properties of two membrane types. We find that the overexpression of the phosphatidylserine lipids in the outer leaflet does not significantly alter the area per lipid, the membrane thickness, the lipid order parameters and the elasticity moduli of the cancer membranes. However, a reduction in the cholesterol concentration leads to clear changes in those quantities, especially decreases in the bending, tilt and twist moduli. This implies that the reduction of cholesterol concentration in the cancer membranes could contribute to the softening of cancer cells.
最近的研究表明，正常细胞和癌细胞之间存在机械差异。由于细胞膜参与了各种重要的过程，我们检验了这样一个假设，即在细胞膜的两个基本变化，即外叶层中磷脂酰丝氨酸脂质的过表达和胆固醇浓度的降低，是否会导致癌细胞的软化。我们采用了十种正常和癌细胞模型，进行了 1 μs 的全原子分子动力学模拟，以比较两种膜类型的结构特性和弹性特性。我们发现，外叶层中磷脂酰丝氨酸脂质的过表达不会显著改变脂双层的面积、膜厚度、脂类序参数和弹性模量。然而，胆固醇浓度的降低会导致这些数量的明显变化，特别是弯曲、倾斜和扭转弹性模量的降低。这意味着癌细胞中胆固醇浓度的降低可能导致癌细胞的软化。
