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线性黏弹区机械负荷下黏液凝胶中的增强微观动力学。

Enhanced microscopic dynamics in mucus gels under a mechanical load in the linear viscoelastic regime.

机构信息

Institute of Polymers, Composites, and Biomaterials, National Research Council of Italy, Naples, 80055 Portici, Italy;

Laboratoire Charles Coulomb, Université Montpellier, CNRS, 34095 Montpellier, France.

出版信息

Proc Natl Acad Sci U S A. 2021 Nov 9;118(45). doi: 10.1073/pnas.2103995118.

Abstract

Mucus is a biological gel covering the surface of several tissues and ensuring key biological functions, including as a protective barrier against dehydration, pathogen penetration, or gastric acids. Mucus biological functioning requires a finely tuned balance between solid-like and fluid-like mechanical response, ensured by reversible bonds between mucins, the glycoproteins that form the gel. In living organisms, mucus is subject to various kinds of mechanical stresses, e.g., due to osmosis, bacterial penetration, coughing, and gastric peristalsis. However, our knowledge of the effects of stress on mucus is still rudimentary and mostly limited to macroscopic rheological measurements, with no insight into the relevant microscopic mechanisms. Here, we run mechanical tests simultaneously to measurements of the microscopic dynamics of pig gastric mucus. Strikingly, we find that a modest shear stress, within the macroscopic rheological linear regime, dramatically enhances mucus reorganization at the microscopic level, as signaled by a transient acceleration of the microscopic dynamics, by up to 2 orders of magnitude. We rationalize these findings by proposing a simple, yet general, model for the dynamics of physical gels under strain and validate its assumptions through numerical simulations of spring networks. These results shed light on the rearrangement dynamics of mucus at the microscopic scale, with potential implications in phenomena ranging from mucus clearance to bacterial and drug penetration.

摘要

黏液是覆盖在若干组织表面的生物凝胶,确保了关键的生物学功能,包括作为防止脱水、病原体穿透或胃酸的保护屏障。黏液的生物功能需要固体样和流体样机械响应之间的精细平衡,这是由形成凝胶的糖蛋白黏蛋白之间的可逆键来保证的。在活生物体中,黏液会受到各种机械应力的影响,例如渗透、细菌穿透、咳嗽和胃蠕动。然而,我们对压力对黏液影响的了解仍然很初步,主要限于宏观流变学测量,而对相关的微观机制则没有深入的了解。在这里,我们同时进行机械测试和猪胃黏液的微观动力学测量。引人注目的是,我们发现适度的剪切应力,即在宏观流变线性范围内,会显著增强黏液在微观水平上的重组,这表现为微观动力学的瞬时加速,可达 2 个数量级。我们通过对弹簧网络的数值模拟来验证我们的假设,从而提出了一个简单但通用的物理凝胶在应变下的动力学模型,对这些发现进行了合理化解释。这些结果揭示了黏液在微观尺度上的重排动力学,这可能对从黏液清除到细菌和药物穿透等现象产生影响。

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