Molecular dynamics study of lipid bilayers modeling the plasma membranes of normal murine thymocytes and leukemic GRSL cells

Abstract

Molecular dynamics (MD) calculations for the plasma membranes of normal murine thymocytes and thymus-derived leukemic GRSL cells in water have been performed under physiological isothermal-isobaric conditions (310.15K and 1 atm) to investigate changes in membrane properties induced by canceration. The model membranes used in our calculations for normal and leukemic thymocytes comprised 23 and 25 kinds of lipids, respectively, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, lysophospholipids, and cholesterol. The mole fractions of the lipids adopted here were based on previously published experimental values. Our calculations clearly showed that the membrane area was increased in leukemic cells, and that the isothermal area compressibility of the leukemic plasma membranes was double that of normal cells. The calculated membranes of leukemic cells were thus considerably bulkier and softer in the lateral direction compared with those of normal cells. The tilt angle of the cholesterol and the conformation of the phospholipid fatty acid tails both showed a lower level of order in leukemic cell membranes compared with normal cell membranes. The lateral radial distribution function of the lipids also showed a more disordered structure in leukemic cell membranes than in normal cell membranes. These observations all show that, for the present thymocytes, the lateral structure of the membrane is considerably disordered by canceration. Furthermore, the calculated lateral self-diffusion coefficient of the lipid molecules in leukemic cell membranes was almost double that in normal cell membranes. The calculated rotational and wobbling autocorrelation functions also indicated that the molecular motion of the lipids was enhanced in leukemic cell membranes. Thus, here we have demonstrated that the membranes of thymocyte leukemic cells are more disordered and more fluid than normal cell membranes.

Methodologies for the analysis of instantaneous lipid diffusion in md simulations of large membrane systems

“…Current published methodologies to visualise the displacement of lipids fall in two categories: Using arrows to represent individual lipid displacement between a time t and a time t+dt 8,9,52,53 .Using lines to connect the different positions of individual lipids over time 8,54,55 . The latter is generally used to present an overview of the global region explored by a lipid while the former is used to depict lateral displacements of lipids in a dedicated area between time t and t+dt .…”

Antioxidant bioactive compounds in tomato fruits at different ripening stages and their effects on normal and cancer cells

“…Indeed, an essential difference between normal and cancer cells is the decrease in the concentration of cholesterol in cancer cell membranes with a considerable change of their physicochemical properties, such as fluidity (Andoh et al, 2013 and references therein). Sucha et al (2013) reported that α-tomatine is not biotransformed in human breast cancer cells, but its concentration significantly decreased in solution since cholesterol forms an insoluble precipitate with α-tomatine.…”

“…This cytosolic enzyme is rapidly released into the cell culture medium upon membrane destabilization, making it a suitable marker of early necrosis and the late stage of apoptosis (Andoh et al, 2013;Chan, Moriwaki, & De Rosa, 2013). We chose HeLa cells as a cancer cell line and HRCE cells as normal cells to evaluate necrosis upon treatment with tomato extracts.…”

Computational modeling and simulation of rupture of membranes and thin films

“…There exists a number of other theoretical and/or computational approaches that may be used to study the mechanical response of structural fabrics [19][20][21][22][23][24][25][26][27][28], fibrous biological tissues [15,[29][30][31][32] and lipid membranes [33][34][35][36][37][38][39][40][41][42] (to cite just a few). Yet, to properly represent anisotropic deformation and rupture at the meso-or macro-scales, we believe that particle-based models (and, to some extent, models based on the network representation of [14][15][16][17]) are among the most suited.…”