Giant Vesicles Mimicking Outer Membrane of Gram-Negative Bacterium

Abstract

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. Past molecular dynamics (MD) simulations demonstrated that the presence of DHSM and high Chol concentration contributes to higher order in lipid membranes. Using the CHARMM36 all-atom force field, this study simulated more complex models of human lens membranes with the inclusion of lysolipids and plasmanyl lipids. Models were developed representing physiological compositions in cataractous lenses aged 7456 years and in healthy lenses aged 2254, 4156, and 6953 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 (S CD), sterol tilt angle, electron density profiles (EDP), bilayer thickness, chain interdigitation, two-dimensional radial distribution functions (2D-RDF), meansquare displacement, 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. S CD parameters suggest similarly, with saturated tails in the hydrophobic core of the membrane having order parameter exceeding 0.4. Vertical packing and acyl tail order increased with both age and cataract. Lateral diffusion decreased with age and cataracts, with the older and cataractous models demonstrating increased long-range structure by the 2D-RDF analysis. Experimental results have found crystallization of Chol in older lenses, which similarly indicates increased order. In future work examining the membrane proteins of the lens, these models can serve as physiologically accurate representations of the lens lipidome.