Virgilio Kelley M, Martin Kyle S, Peirce Shayn M, Blemker Silvia S
Department of Biomedical Engineering , University of Virginia , Charlottesville, VA 22908 , USA.
Department of Biomedical Engineering , University of Virginia , Charlottesville, VA 22908 , USA ; Department of Orthopaedic Surgery , University of Virginia , Charlottesville, VA 22908 , USA ; Department of Mechanical and Aerospace Engineering , University of Virginia , Charlottesville, VA 22908 , USA.
Interface Focus. 2015 Apr 6;5(2):20140080. doi: 10.1098/rsfs.2014.0080.
Computational models have been increasingly used to study the tissue-level constitutive properties of muscle microstructure; however, these models were not created to study or incorporate the influence of disease-associated modifications in muscle. The purpose of this paper was to develop a novel multiscale muscle modelling framework to elucidate the relationship between microstructural disease adaptations and modifications in both mechanical properties of muscle and strain in the cell membrane. We used an agent-based model to randomly generate new muscle fibre geometries and mapped them into a finite-element model representing a cross section of a muscle fascicle. The framework enabled us to explore variability in the shape and arrangement of fibres, as well as to incorporate disease-related changes. We applied this method to reveal the trade-offs between mechanical properties and damage susceptibility in Duchenne muscular dystrophy (DMD). DMD is a fatal genetic disease caused by a lack of the transmembrane protein dystrophin, leading to muscle wasting and death due to cardiac or pulmonary complications. The most prevalent microstructural variations in DMD include: lack of transmembrane proteins, fibrosis, fatty infiltration and variation in fibre cross-sectional area. A parameter analysis of these variations and case study of DMD revealed that the nature of fibrosis and density of transmembrane proteins strongly affected the stiffness of the muscle and susceptibility to membrane damage.
计算模型已越来越多地用于研究肌肉微观结构的组织水平本构特性；然而，这些模型并非用于研究或纳入疾病相关的肌肉改变的影响。本文的目的是开发一种新型的多尺度肌肉建模框架，以阐明微观结构疾病适应性与肌肉力学性能和细胞膜应变变化之间的关系。我们使用基于代理的模型随机生成新的肌纤维几何形状，并将它们映射到代表肌肉束横截面的有限元模型中。该框架使我们能够探索纤维形状和排列的变异性，并纳入与疾病相关的变化。我们应用此方法揭示杜氏肌营养不良症（DMD）中力学性能与损伤易感性之间的权衡。DMD是一种致命的遗传性疾病，由跨膜蛋白肌营养不良蛋白缺乏引起，导致肌肉萎缩并因心脏或肺部并发症而死亡。DMD中最常见的微观结构变化包括：跨膜蛋白缺乏、纤维化、脂肪浸润和纤维横截面积变化。对这些变化的参数分析和DMD的案例研究表明，纤维化的性质和跨膜蛋白的密度强烈影响肌肉的刚度和对膜损伤的易感性。
