Predicted Decrease in Membrane Oxygen Permeability with Addition of Cholesterol
Aberrations in cholesterol homeostasis are associated with several diseases that can be linked to changes in cellular oxygen usage. Prior biological and physical studies have suggested that membrane cholesterol content can modulate oxygen delivery, but questions of magnitude and biological significance remain open for further investigation. Here, we use molecular dynamics simulations in a first step toward reexamining the rate impact of cholesterol on the permeation of oxygen through phospholipid bilayers. The simulation models are closely compared with published electron paramagnetic resonance (EPR) oximetry measurements. The simulations predict an oxygen permeability reduction due to cholesterol but also suggest that the EPR experiments may have underestimated resistance to oxygen permeation in the phospholipid headgroup region.
KeywordsMolecular dynamics simulation Oximetry Electron paramagnetic resonance (EPR) Resistance to permeation Tempocholine
We thank Ross Walker and Benjamin Madej for providing advance access to the cholesterol parameters used in this study. James Ryan Bredin developed the O2 parameters used in this work. Daniel Lyons contributed valuable computing expertise. The molecular images were generated using PyMOL software , and DataThief software  was used to infer the experimental values reported in Fig. 2.1b from published plots. SCP thanks James Kindt and Snežna Rogelj for professional mentoring. This work was supported by the NIH under NIGMS grant P20GM103451 and by a gift from the Glendorn Foundation. The content is solely the responsibility of the authors. We used computing resources of TACC at UT Austin, accessed through XSEDE (funded by NSF grant ACI-1053575), as well as the EXXACT MD SimCluster (“Electra”) at New Mexico Tech.
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