Modeling Mechanical Cell-Matrix Interactions in Articular Cartilage

海德尔0211154 研究者正在开发关节软骨中细胞和细胞外基质之间力学相互作用的多相模型。 分析和数值方法的组合用于解决：（1）接触问题，模型实验用于确定孤立的细胞（软骨细胞）和细胞-基质（软骨）单元的力学性能，（2）界面问题，模型局部细胞-基质力学的软骨在体内，和（3）快速边界积分模型的机械信号传输的组织层填充许多细胞。 通过与骨科研究实验室的合作，研究者开发的模型被应用于：（a）使用体外微量移液管测试和视频显微镜确定细胞和组织外植体的材料特性，以及（B）模拟局部细胞-基质力学并与组织层动态载荷的共聚焦显微镜进行比较。 本项目的一个基本目标是量化局部细胞力学对外部载荷的依赖性。 通过将细胞代谢活动的实验测量与局部细胞环境的机械成分相关联，分析了组织代谢与细胞机械之间的复杂关系。 在软骨材料和几何特性的变化，内部和跨各种组织种群，也被纳入模型。 该项目有助于理解力学在维持细胞外基质中的作用，以及骨关节炎引起的衰老相关基质变性。 关节软骨是膝、肩、髋等关节的主要承重组织。 软骨退化会导致骨关节炎，这是一种影响数百万美国人的痛苦疾病，主要与衰老有关。 在反复的负荷下，软骨的结构基质处于一种持续的更新状态，这种状态由称为软骨细胞的专门细胞调节。 值得注意的是，这些细胞合成基质成分，但与大脑没有神经联系。 因此，修复结构基质的细胞代谢活动高度依赖于局部细胞环境。 在这个项目中，一个数学模型与一个整形外科研究实验室合作，以了解机械力在软骨维护中的作用。 在细胞水平上，软骨中的力是由固体和流体力学与能量耗散的复杂耦合引起的，这项工作的结果预测了细胞尺度上局部力对外部载荷的依赖性。 局部力预测有助于定量描述细胞代谢活动与细胞力学之间的复杂关系。 结合各种组织群的相关实验，这些模型有助于理解这些非凡的细胞如何在一生中维持软骨，以及骨关节炎中软骨的结构退化是如何开始的。

Haider0211154 The investigator is developing multiphasic models formechanical interactions between the cells and extracellularmatrix in articular cartilage. A combination of analytical andnumerical methods are used to solve: (1) contact problems thatmodel experiments used to determine mechanical properties ofisolated cell (chondrocyte) and cell-matrix (chondron) units, (2)interface problems that model local cell-matrix mechanics of thechondron in vivo, and (3) fast boundary integral models fortransmission of mechanical signals in a tissue layer populatedwith many cells. Through collaboration with an orthopaedicresearch lab, the models developed by the investigator are beingapplied to: (a) the determination of material properties of celland tissue explants using in-vitro micropipette testing and videomicroscopy, and (b) the simulation of local cell-matrix mechanicsand comparison to confocal microscopy of dynamic loading in atissue layer. A fundamental goal of this project is to quantifythe dependence of local cell mechanics on external loading. Bycorrelating experimental measurements of cell metabolic activityto mechanical components of the local cell environment, thecomplex relationship between tissue metabolism and cell mechanicsis analyzed. Variations in chondron material and geometricproperties, within and across a variety of tissue populations,are also incorporated into the models. This project contributesto understanding of the role of mechanics in maintenance of theextracellular matrix, and associated matrix degeneration withaging due to osteoarthritis. Articular cartilage is the primary load-bearing tissue injoints such as the knee, shoulder and hip. Degeneration ofcartilage leads to osteoarthritis, a painful condition thataffects millions of Americans and is predominantly associatedwith aging. Under repeated loading, the structural matrix ofcartilage is in a continual state of turnover that is regulatedby specialized cells called chondrocytes. These cells synthesizematrix components yet, remarkably, have no neural connection tothe brain. As a result, cell metabolic activities directed atrepairing the structural matrix are highly dependent on the localcell environment. In this project, a mathematical modelercollaborates with an orthopaedic research lab to understand therole of mechanical forces in the maintenance of cartilage. Atthe cellular level, forces in cartilage result from a complexcoupling of solid and fluid mechanics with energy dissipation.Results of this work predict the dependence of local forces atthe cellular scale on external loading. Local force predictionsfacilitate a quantitative description of the complex relationshipbetween cell metabolic activity and cell mechanics. Inconjunction with associated experiments for a variety of tissuepopulations, the models lead to an understanding of how theseremarkable cells can maintain cartilage over the course of alifetime, and how structural degeneration of cartilage isinitiated in osteoarthritis.