Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts02139, United States.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts02139, United States.
Biomacromolecules. 2023 Feb 13;24(2):628-639. doi: 10.1021/acs.biomac.2c01016. Epub 2023 Feb 2.
Simulating native mucus with model systems such as gels made from reconstituted mucin or commercially available polymers presents experimental advantages including greater sample availability and reduced inter- and intradonor heterogeneity. Understanding whether these gels reproduce the complex physical and biochemical properties of native mucus at multiple length scales is critical to building relevant experimental models, but few systematic comparisons have been reported. Here, we compared bulk mechanical properties, microstructure, and biochemical responses of mucus from different niches, reconstituted mucin gels (with similar pH and polymer concentrations as native tissues), and commonly used commercially available polymers. To evaluate gel properties across these length scales, we used small-amplitude oscillatory shear, single-particle tracking, and microaffinity chromatography with small analytes. With the exception of human saliva, the mechanical response of mucin gels was qualitatively similar to that of native mucus. The transport behavior of charged peptides through native mucus gels was qualitatively reproduced in gels composed of corresponding isolated mucins. Compared to native mucus, we observed substantial differences in the physicochemical properties of gels reconstituted from commercially available mucins and the substitute carboxymethylcellulose, which is currently used in artificial tear and saliva treatments. Our study highlights the importance of selecting a mucus model system guided by the length scale relevant to the scientific investigation or disease application.
用模型系统模拟天然黏液，如由重组黏蛋白或市售聚合物制成的凝胶，具有实验优势，包括更大的样品可用性和减少供体间和供体内的异质性。了解这些凝胶是否在多个长度尺度上再现天然黏液的复杂物理和生化特性对于构建相关实验模型至关重要，但很少有系统的比较报告。在这里，我们比较了来自不同生态位的黏液、重组黏蛋白凝胶（具有与天然组织相似的 pH 值和聚合物浓度）和常用的市售聚合物的整体力学性能、微观结构和生化反应。为了评估这些长度尺度上的凝胶特性，我们使用了小振幅振荡剪切、单颗粒跟踪和微亲和层析以及小分子分析物。除了人唾液外，黏蛋白凝胶的力学响应与天然黏液的定性相似。通过小分析物的微亲和层析，通过天然黏液凝胶中带电荷的肽的传输行为在由相应的分离黏蛋白组成的凝胶中得到了定性再现。与天然黏液相比，我们观察到由市售黏蛋白和替代羧甲基纤维素（目前用于人工泪液和唾液治疗）组成的凝胶的物理化学性质存在显著差异。我们的研究强调了根据科学研究或疾病应用的相关长度尺度选择黏液模型系统的重要性。
