Vervust Wouter, Safaei Sina, Witschas Katja, Leybaert Luc, Ghysels An
Institute of Biomedical Engineering and Technology, Biophysical Models for Medical Applications group, Ghent University, Ghent B9000, Belgium.
Department of Basic and Applied Medical Sciences, Physiology Group, Ghent University, Ghent B9000, Belgium.
Proc Natl Acad Sci U S A. 2025 May 20;122(20):e2422437122. doi: 10.1073/pnas.2422437122. Epub 2025 May 16.
Oxygen is crucial for mitochondrial energy production in neurons and is efficiently stored and transported within the hydrophobic core of phospholipid bilayers. Using a diffusive model derived from molecular dynamics simulations, we demonstrate that oxygen storage in a bilayer follows first-order kinetics, which can be effectively represented by an RC (resistor-capacitor) circuit. For myelin, with multiple bilayers, oxygen transport is modeled through a ladder network of RC circuits, where oxygen permeation resistance and oxygen storage capacity scale linearly with bilayer count. Meanwhile, the characteristic time constant scales quadratically with myelin thickness, e.g. enhancing the characteristic time constant from 30 ns for one 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer to 506 s for 200 POPC bilayers. This model shows that myelin sheaths serve as compact oxygen reservoirs, dampening sudden oxygen changes due to their slower release kinetics. During increased neuronal activity, the model suggests that myelination extends the ability to sustain elevated oxygen demand, implying a buffering role for myelin against oxygen fluctuations, while the need for vascular response remains critical in maintaining long-term oxygen homeostasis.
氧气对于神经元中的线粒体能量产生至关重要，并且能在磷脂双分子层的疏水核心内有效储存和运输。我们利用从分子动力学模拟得出的扩散模型证明，双分子层中的氧气储存遵循一级动力学，这可以用一个RC（电阻-电容）电路有效地表示。对于具有多个双分子层的髓鞘，氧气运输通过RC电路的梯形网络进行建模，其中氧气渗透阻力和氧气储存容量与双分子层数呈线性比例关系。同时，特征时间常数与髓鞘厚度呈二次方比例关系，例如，将特征时间常数从一个1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱（POPC）双分子层的30纳秒提高到200个POPC双分子层的506秒。该模型表明，髓鞘起着紧密的氧气储存库的作用，因其较慢的释放动力学而缓冲了氧气的突然变化。在神经元活动增加期间，该模型表明髓鞘形成扩展了维持升高的氧气需求的能力，这意味着髓鞘对氧气波动具有缓冲作用，而血管反应对于维持长期氧气稳态仍然至关重要。
