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Is the cholesterol bilayer domain a barrier to oxygen transport into the eye lens? Biochim Biophys Acta Biomembr 2018 Feb;1860(2):434-441

Date

10/29/2017

Pubmed ID

29079282

Pubmed Central ID

PMC5732854

DOI

10.1016/j.bbamem.2017.10.020

Abstract

In the eye lens, the oxygen partial pressure is very low and the cholesterol (Chol) content in cell membranes is very high. Disturbance of these quantities results in cataract development. In human lens membranes, both bulk phospholipid-Chol domains and the pure Chol bilayer domains (CBDs) were experimentally detected. It is hypothesized that the CBD constitutes a significant barrier to oxygen transport into the lens. Transmembrane profiles of the oxygen diffusion-concentration product, obtained with electron paramagnetic resonance spin-labeling methods, allow evaluation of the oxygen permeability (PM) of phospholipid membranes but not the CBD. Molecular dynamics simulation can independently provide components of the product across any bilayer domain, thus allowing evaluation of the PM across the CBD. Therefore, to test the hypothesis, MD simulation was used. Three bilayers containing palmitoyl-oleoyl-phosphorylcholine (POPC) and Chol were built. The pure Chol bilayer modeled the CBD, the 1:1 POPC-Chol bilayer modeled the bulk membrane in which the CBD is embedded, and the POPC bilayer was a reference. To each model, 200 oxygen molecules were added. After equilibration, the oxygen concentration and diffusion profiles were calculated for each model and multiplied by each other. From the respective product profiles, the PM of each bilayer was calculated. Favorable comparison with experimental data available only for the POPC and POPC-Chol bilayers validated these bilayer models and allowed the conclusion that oxygen permeation across the CBD is ~10 smaller than across the bulk membrane, supporting the hypothesis that the CBD is a barrier to oxygen transport into the eye lens.

Author List

Plesnar E, Szczelina R, Subczynski WK, Pasenkiewicz-Gierula M

Author

Witold K. Subczynski PhD Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Biological Transport
Cataract
Cell Membrane
Cholesterol
Diffusion
Electron Spin Resonance Spectroscopy
Humans
Kinetics
Lens, Crystalline
Lipid Bilayers
Molecular Dynamics Simulation
Oxygen
Phosphatidylcholines
Spin Labels