AI 中文总结
本研究通过粗粒化模型揭示化学交联蛋白质水凝胶中动态解折叠与凝胶后重排如何产生介观异质性，为设计新型生物材料提供预测性理解。
AI 中文摘要
蛋白质水凝胶设计的合理化对于制造针对一系列医疗和保健应用（如组织工程、伤口愈合和生物传感器）的定制功能材料至关重要。蛋白质解折叠的动态过程能显著影响所得凝胶的结构和行为——单个蛋白质构建块的构象变化影响整体凝胶，而整体条件的变化又影响单个蛋白质的运动和响应方式。为了表征和控制蛋白质水凝胶，必须建立多长度尺度的图像，以便理解这种复杂的相互作用。我们开发了一个粗粒化计算模型，以研究化学交联蛋白质水凝胶内动态解折叠的基本方面，重点关注凝胶化期间和之后的介观结构。通过将蛋白质解折叠简化为单个动态步骤，我们能够创建由粗粒化蛋白质形成的异质性网络。我们观察到演化的水凝胶由高密度蛋白质簇区域组成，由于局部拥挤效应，这些区域具有较低的解折叠程度，并通过低密度链状区域相互连接，这些区域具有较高浓度的解折叠蛋白质。系统性地改变单个蛋白质解折叠的能垒高度表明，其对以分形维数和相关长度表征的介观结构影响较弱。相反，在凝胶经历持续构象弛豫后，这些参数的测量变化更大。这项工作证明了粗粒化建模在捕获交联可解折叠蛋白质的异质性介观网络方面的有效性。通过该模型，对蛋白质水凝胶结构和行为的预测性理解得到增强，并将加速新型生物材料的设计。
英文摘要
The rationalization of protein hydrogel design is essential in creating bespoke and functional materials for a range of medical and healthcare applications, such as tissue engineering, wound healing and bio-sensors. The dynamic process of protein unfolding can significantly influence the resultant gel structure and behaviour - conformational changes in individual protein building blocks affect the bulk gel, whilst changes to bulk conditions influence how individual proteins move and respond. In order to characterize and control protein hydrogels, a multi-lengthscale picture must be built so that this complex interplay can be understood. We develop a coarse-grained computational model to investigate fundamental aspects of dynamic unfolding within chemically crosslinked protein hydrogels, focussing on the mesoscale structure during and after gelation. In simplifying protein unfolding to a single dynamic step, we are able to create a heterogeneous network formed of coarse-grained proteins. We observe evolving hydrogels consisting of regions of high-density protein clusters with a low degree of unfolding due to local crowding effects, interconnected by low-density stranded regions with a higher concentration of unfolded proteins. Systematically varying the barrier height for single protein unfolding demonstrates a weak influence on the mesoscale structure as characterised by fractal dimension and correlation length. Conversely, the measured changes in these parameters are greater after the gel experiences sustained conformational relaxation. This work demonstrates the effectiveness of coarse-grained modelling in capturing the heterogeneous mesoscale network of crosslinked unfoldable proteins. A greater predictive understanding of the structure and behaviour of protein hydrogels is gained through this model and will accelerate the design of novel biomaterials.
Comments9 pages, 8 figures
