Department of Chemistry, New Mexico Institute of Mining and Technology (New Mexico Tech), Socorro, NM, USA.
Adv Exp Med Biol. 2024;1463:9-14. doi: 10.1007/978-3-031-67458-7_2.
Building on an extensive history of physiological and systems-oriented modelling, my group and others have recently used molecular simulation studies to understand oxygen (O) transport and localisation. Molecular simulations enable biophysical insight into processes difficult to study with experiments alone and are sometimes described as a "computational microscope." Our work has emphasised lipid membrane contributions to oxygen diffusion and uptake, suggesting that lipid-based pathways along membranes and lipid deposits are likely to accelerate diffusive transport through cells and tissues. Moreover, the lipid and fluid fractions of the tissue are expected to be primary determinants of the local oxygen partial pressure (pO) as well as the oxygen permeability. Measurements using molecular probes can be influenced by the local molecular environment, due to differential solubility of both the probe and the oxygen molecules in various components of the cell's complex solvent system. The biomolecular simulation work complements experimental studies, which enable evaluation of the models' accuracy and their applicability to real biological systems. Further work is needed to assess fully the possible influence of nanoscale crowders and obstacles (especially protein molecules) on tissue-level diffusive transport of oxygen. Likewise, water-rich carbohydrate layers, such as the glycocalyx, should be evaluated as potential barriers to oxygen transport. Insights gained through biophysical modelling studies could be broadly relevant to clinical phenomena affected by tissue oxygenation, such as tumour radiotherapy, ischaemia, neuropathy, and wound healing.
基于广泛的生理和系统导向建模历史，我和其他研究小组最近使用分子模拟研究来理解氧（O）的运输和定位。分子模拟使人们能够深入了解仅凭实验难以研究的过程，有时被描述为“计算显微镜”。我们的工作强调了脂质膜对氧扩散和摄取的贡献，表明沿着膜的基于脂质的途径和脂质沉积物可能会加速细胞和组织中的扩散运输。此外，组织的脂质和流体部分预计是局部氧分压（pO）以及氧通透性的主要决定因素。由于分子探针在细胞复杂溶剂系统的各个组成部分中的溶解度不同，因此使用分子探针进行的测量可能会受到局部分子环境的影响。生物分子模拟工作补充了实验研究，可以评估模型的准确性及其在真实生物系统中的适用性。需要进一步的工作来评估纳米级拥挤物和障碍物（特别是蛋白质分子）对组织水平氧扩散传输的可能影响。同样，富含水的碳水化合物层，如糖萼，应被评估为氧运输的潜在障碍。通过生物物理建模研究获得的见解可能与受组织氧合影响的临床现象广泛相关，例如肿瘤放疗、缺血、神经病变和伤口愈合。
