Abstract
Molecular oxygen delivery to mitochondria is essential for aerobic metabolism. Oxygen must diffuse across multiple membranes on the cellular and tissue levels. A steady supply of oxygen is essential for normal cellular bioenergetics, so even modest membrane resistance could generate intracellular hypoxia and promote pathological shifts in energy metabolism. The extent to which the membranes resist oxygen diffusion depends on their composition and physical properties. In particular, the presence of cholesterol is known to slow oxygen diffusion, but the physical details of the phenomenon remain to be clarified. We have undertaken a systematic study of oxygen transport thermodynamics, using GPU-accelerated, all-atom molecular dynamics simulations. From microsecond-timescale, unrestrained simulations, we have calculated free energy and diffusion coefficient profiles tracking oxygen permeation in model bilayer systems consisting of POPC and/or 0 to 100 mol% cholesterol. With increasing cholesterol content, we observe a steady and dramatic increase in the activation energy associated with membrane crossing. Ongoing study addresses the kinetic impact and biological significance of this diffusional barrier.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
