Computational Biomechanics Modeling of Inflammation

项目摘要/摘要 支配宇宙的物理定律也支配着活组织的健康功能，以及 疾病的发生和发展。从历史上看，生物医学研究界忽视了 力学在许多发展、病理和适应过程中的作用。在我的研究小组里，计算机- 在巴黎圣母院(指挥实验室)，我们在力学的交叉点工作， 计算和生物学，研究组织和器官的耦合生物力学行为，特别是 在生长和重塑期间。在这项提案中，我们的工作旨在将我们的工作扩展到Infl炎性肿胀的研究。 与生长类似，Infl变形和肿胀涉及质量的局部变化(例如，由于InflUX 细胞)，这可以表现为体积的变化。而外部肿胀通常被用作不足的指标 在fl氨化过程中，来自周围组织的限制也可以限制肿胀，反而会导致肿胀增加 在压力下。此外，在fl中，氨基化可以极大地改变组织的细胞组成。在fl中，拼写是 广泛分布于不同组织，这些后遗症对诊断、诊断和治疗有重要意义。 发展，和治疗不同的疾病。我们将开发新的Infl计算模型 和肿胀，1)允许细胞行为在空间上、时间上和细胞类型之间变化；2)解释机械 肿胀组织与周围组织之间的相互作用；以及3)以便于 校准、验证，并与实验进行比较。这项工作将为小规模探测提供工具 超越大范围膨胀的现象，探索个别参数的影响，并检验假设 关于Infl在硅胶中的生物力学问题。 1

Project Summary/Abstract The physical laws that govern the universe also govern the healthy functioning of living tissues, as well as the genesis and development of diseases. Historically, the biomedical research community has overlooked the role of mechanics in many developmental, pathological, and adaptive processes. In my research group, the Compu- tational Mechanics of Morphology at Notre Dame (CoMMaND Lab), we work at the intersection of mechanics, computation, and biology, to investigate the coupled bio-mechanical behaviors of tissues and organs, particularly during growth and remodeling. In this proposal, we aim to extend our work to the study of inflammatory swelling. Similarly to growth, inflammation and swelling involve local changes in mass (for instance, due to an influx of cells) which can manifest as changes in volume. While external swelling is often used as an indicator of under- lying inflammation, constraints from surrounding tissue can also restrict swelling and instead result in increases in pressure. In addition, inflammation can drastically change the cellular composition of a tissue. Inflammation is widespread among different tissues, and these sequelae can have important implications for the diagnosis, de- velopment, and treatment of different diseases. We will developing novel computational models of inflammation and swelling that 1) allow for cell behavior to vary spatially, temporally, and by cell type; 2) account for mechanical interactions between the swelling tissue and surrounding tissues; and 3) report results in a way that facilitates calibration, validation, and comparisons with experimental. This work will provide tools for probing small-scale phenomena beyond large-scale swelling, exploring the effects of individual parameters, and testing hypotheses regarding the biomechanics of inflammation in silico. 1