Globular folded proteins are versatile nanoscale building blocks to create biomaterials with mechanical robustness and inherent biological functionality due to their specific and well-defined folded structures. Modulating the nanoscale unfolding of protein building blocks during network formation (in situ protein unfolding) provides potent opportunities to control the protein network structure and mechanics. Here, we control protein unfolding during the formation of hydrogels constructed from chemically cross-linked maltose binding protein using ligand binding and the addition of cosolutes to modulate protein kinetic and thermodynamic stability. Bulk shear rheology characterizes the storage moduli of the bound and unbound protein hydrogels and reveals a correlation between network rigidity, characterized as an increase in the storage modulus, and protein thermodynamic stability. Furthermore, analysis of the network relaxation behavior identifies a crossover from an unfolding dominated regime to an entanglement dominated regime. Control of in situ protein unfolding and entanglement provides an important route to finely tune the architecture, mechanics, and dynamic relaxation of protein hydrogels. Such predictive control will be advantageous for future smart biomaterials for applications which require responsive and dynamic modulation of mechanical properties and biological function.

中文翻译：

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通过调节凝胶化后松弛中的纳米级展开和缠结来调节蛋白质水凝胶力学

球状折叠蛋白是多功能的纳米级构建块，由于其特定且明确定义的折叠结构，可用于创建具有机械强度和固有生物功能的生物材料。在网络形成过程中调节蛋白质构建块的纳米级展开（原位蛋白质展开）为控制蛋白质网络结构和力学提供了有力的机会。在这里，我们使用配体结合和添加共溶质来调节蛋白质动力学和热力学稳定性，从而在由化学交联的麦芽糖结合蛋白构建的水凝胶形成过程中控制蛋白质展开。体积剪切流变学表征了结合和未结合的蛋白质水凝胶的储能模量，并揭示了网络刚性（其特征是储能模量的增加）与蛋白质热力学稳定性之间的相关性。此外，对网络松弛行为的分析确定了从展开主导机制到纠缠主导机制的交叉。就地控制蛋白质展开和缠结为微调蛋白质水凝胶的结构、力学和动态松弛提供了重要途径。这种预测控制将有利于未来智能生物材料的应用，这些材料需要对机械性能和生物功能进行响应和动态调制。