将胶原纤维降解建模为基质微结构的函数
Modeling collagen fibril degradation as a function of matrix microarchitecture
AI总结：
本文通过单纤维晶格模型与多纤维三维布朗动力学模拟，揭示胶原基质微结构通过影响酶的非均匀分布决定其可降解性，并经体外实验验证。
摘要：
胶原降解是组织重塑的基本过程。胶原纤维网络的微结构在发育、衰老和疾病过程中会发生变化，这种微结构变化通常伴随基质可降解性的改变。在体外实验中，相同浓度但不同微结构的胶原基质也表现出不同的降解速率。不同微结构如何影响基质降解？为回答这一问题，我们开发了一个胶原降解的计算模型。我们首先建立了一个晶格模型，用于描述单根纤维尺度上的胶原降解。随后，我们将该模型扩展，通过多纤维三维基质中酶的布朗动力学模拟来研究微结构的作用，并预测基质的可降解性。我们的模拟预测，纤维周围的酶分布是非均匀的，并且依赖于基质的微结构。这种酶分布的非均匀性可导致不同微结构基质具有不同程度的可降解性。我们利用不同微结构的合成胶原凝胶进行了体外实验，对模型预测进行了验证。实验表明，胶原的降解确实取决于基质结构和纤维厚度。总之，我们的研究表明，胶原基质的微结构是其可降解性的重要决定因素。
英文摘要：
Collagenolytic degradation is a process fundamental to tissue remodeling. The microarchitecture of collagen fibril networks changes during development, aging, and disease. Such changes to microarchitecture are often accompanied by changes in matrix degradability. In vitro, collagen matrices of the same concentration but different microarchitectures also vary in degradation rate. How do different microarchitectures affect matrix degradation? To answer this question, we developed a computational model of collagen degradation. We first developed a lattice model that describes collagen degradation at the scale of a single fibril. We then extended this model to investigate the role of microarchitecture using Brownian dynamics simulation of enzymes in a multi-fibril three dimensional matrix to predict its degradability. Our simulations predict that the distribution of enzymes around the fibrils is non-uniform and depends on the microarchitecture of the matrix. This non-uniformity in enzyme distribution can lead to different extents of degradability for matrices of different microarchitectures. Our model predictions were tested using in vitro experiments with synthesized collagen gels of different microarchitectures. Experiments showed that indeed degradation of collagen depends on the matrix architecture and fibril thickness. In summary, our study shows that the microarchitecture of the collagen matrix is an important determinant of its degradability.
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