Empirical and Theoretical Analysis of Particle Diffusion in Mucus
Empirical and Theoretical Analysis of Particle Diffusion in Mucus
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DOI：
10.3389/fphy.2021.594306
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发表时间：
2021-11-23
影响因子：
3.1
通讯作者：
Luque, Antoni
中科院分区：
文献类型：
--
作者：
Cobarrubia, Antonio;Tall, Jarod;Luque, Antoni
粘液是一种复杂的液体，覆盖在动物的多个器官上。各种物理化学性质可以改变粘液中微观颗粒的扩散，影响药物递送、病毒感染和疾病发展。然而，这些物理化学性质在颗粒扩散中的同时作用仍然是难以捉摸的。在这里，我们分析了106个已发表的实验，以确定控制粘液中颗粒扩散的最主要因素。有效的扩散-使用一秒的采样时间窗口在整个实验中定义-跨越7个数量级，从10（-5）到10（2）μ m（2）/s。单变量和多变量统计分析确定的异常指数（均方位移的对数斜率）作为有效扩散的最强预测因子，揭示了解释89%的方差的指数关系。理论标度分析表明，一个更强的相关性的异常指数超过广义扩散常数发生采样时间两个数量级大于特征分子（或本地）位移时间。这一结果预测，在这些时间尺度上，控制异常指数的分子特性，如颗粒-粘液解结合时间或颗粒与筛孔尺寸比，将是粘液中颗粒被动微观流变学中涉及的最相关的物理化学因素。我们的研究结果与以下事实形成对比：只有三分之一的研究测量了异常指数，并且大多数实验没有报告预测主导粘液中颗粒运动的相关分子特性。我们工作的理论基础可以外推到其他系统，为确定调节粘液和其他聚合物流体中颗粒流动性的主导分子机制提供指导。
Mucus is a complex fluid that coats multiple organs in animals. Various physicochemical properties can alter the diffusion of microscopic particles in mucus, impacting drug delivery, virus infection, and disease development. The simultaneous effect of these physicochemical properties in particle diffusion, however, remains elusive. Here, we analyzed 106 published experiments to identify the most dominant factors controlling particle diffusion in mucus. The effective diffusion-defined using a one-second sampling time window across experiments-spanned seven orders of magnitude, from 10(-5) to 10(2) mu m(2)/s. Univariate and multivariate statistical analyses identified the anomalous exponent (the logarithmic slope of the mean-squared displacement) as the strongest predictor of effective diffusion, revealing an exponential relationship that explained 89% of the variance. A theoretical scaling analysis revealed that a stronger correlation of the anomalous exponent over the generalized diffusion constant occurs for sampling times two orders of magnitude larger than the characteristic molecular (or local) displacement time. This result predicts that at these timescales, the molecular properties controlling the anomalous exponent, like particle-mucus unbinding times or the particle to mesh size ratio, would be the most relevant physicochemical factors involved in passive microrheology of particles in mucus. Our findings contrast with the fact that only one-third of the studies measured the anomalous exponent, and most experiments did not report the associated molecular properties predicted to dominate the motion of particles in mucus. The theoretical foundation of our work can be extrapolated to other systems, providing a guide to identify dominant molecular mechanisms regulating the mobility of particles in mucus and other polymeric fluids.