Modeling collagen fibril degradation as a function of matrix microarchitecture†

IF 2.9 3区 化学 Q3 CHEMISTRY, PHYSICAL
Soft Matter Pub Date : 2024-11-18 DOI:10.1039/D4SM00971A
Bhanjan Debnath, Badri Narayanan Narasimhan, Stephanie I. Fraley and Padmini Rangamani
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引用次数: 0

Abstract

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 a matrix, the pore size and fibril characteristics such as length, diameter, number, orientation, and curvature are the major variables that define the microarchitecture. 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 simulations predict that for the same enzyme concentration and collagen concentration, a matrix with thicker fibrils degrades more than that with thinner fibrils. Our model predictions were tested using in vitro experiments with synthetic 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.

Abstract Image

作为基质微结构函数的胶原纤维降解模型。
胶原蛋白溶解降解是组织重塑的基本过程。胶原纤维网络的微观结构会在发育、衰老和疾病过程中发生变化。这种微结构的变化往往伴随着基质降解性的变化。在基质中,孔隙大小和纤维特征(如长度、直径、数量、方向和曲率)是定义微结构的主要变量。在体外,浓度相同但微结构不同的胶原蛋白基质在降解率方面也存在差异。不同的微结构如何影响基质降解?为了回答这个问题,我们开发了胶原降解的计算模型。我们首先开发了一个晶格模型,用于描述单纤维尺度的胶原降解。然后,我们扩展了这一模型,利用布朗动力学模拟多纤维三维基质中的酶来预测其降解性,从而研究微结构的作用。我们的模拟预测,酶在纤维周围的分布是不均匀的,取决于基质的微结构。酶分布的这种不均匀性会导致不同微结构的基质具有不同程度的降解性。根据我们的模拟预测,在酶浓度和胶原蛋白浓度相同的情况下,纤维较粗的基质比纤维较细的基质降解得更快。我们使用不同微结构的合成胶原蛋白凝胶进行了体外实验,对模型预测进行了检验。实验表明,胶原蛋白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,胶原蛋白基质的微观结构是决定其降解性的重要因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Soft Matter
Soft Matter 工程技术-材料科学:综合
CiteScore
6.00
自引率
5.90%
发文量
891
审稿时长
1.9 months
期刊介绍: Soft Matter is an international journal published by the Royal Society of Chemistry using Engineering-Materials Science: A Synthesis as its research focus. It publishes original research articles, review articles, and synthesis articles related to this field, reporting the latest discoveries in the relevant theoretical, practical, and applied disciplines in a timely manner, and aims to promote the rapid exchange of scientific information in this subject area. The journal is an open access journal. The journal is an open access journal and has not been placed on the alert list in the last three years.
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