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Updated: Nov 6, 2025

Enrichment of Mammalian Tissues and Xenopus Oocytes with Cholesterol
Published on: March 25, 2020
Updated Evaluation of Cholesterol's Influence on Membrane Oxygen Permeability
Rachel J Dotson1, Emily McClenahan1, Sally C Pias2
1Department of Chemistry, New Mexico Institute of Mining and Technology (New Mexico Tech), Socorro, NM, USA.
Abstract:
There is a surprising gap in knowledge regarding the mechanism of oxygen (O2) diffusional delivery at the level of tissues and cells. Yet, the effectiveness of tumor radiotherapy, the success of tissue engineering, and healthy metabolism all require ample intracellular oxygen. Tissue-level diffusion takes place in a complex and crowded macromolecular environment. Cholesterol-rich cellular membranes have been thought to reduce oxygen flux. Here, we use atomistic molecular dynamics simulations to update prior estimates of bilayer permeability and related parameters for 1-palmitoyl,2-oleoylphosphatidylcholine (POPC) and POPC/cholesterol bilayers, using a modified O2 model with improved membrane-water partitioning behavior. This work estimates an oxygen permeability coefficient of 15 ± 1 cm/s for POPC and 11.5 ± 0.4 cm/s for POPC/cholesterol (1:1 molecular ratio) at 37 °C. The permeability of POPC is found to be ~1/3 that of a water layer of similar thickness, and the permeability of POPC/cholesterol is estimated to be 20-30% below that of POPC. Void pathway visualization and free energy data support channeling of oxygen toward the center of cholesterol-incorporating membranes, while partition coefficient data suggest reduced membrane solubility of oxygen due to cholesterol. Further study is needed to understand whether diffusion pathway changes due to cholesterol and other molecular compositional factors influence oxygen availability within tissue.
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