Mathematical Modeling and Computational Analysis of Cell and Tissue Movement

Othmer和Stolarska的研究人员建立并分析了单个、非相互作用的阿米巴细胞中的信号转导、方向感知和运动的数学模型，并将基于个体的模型纳入了细胞强烈相互作用的组织状细胞聚集体运动的模型中。Dictyostelialdiscoideum细胞黏液霉菌被用作模型系统，因为它既体现了单个细胞的自由运动，也体现了聚集体的集体情感，并被广泛用作研究细胞运动的模型实验系统。在数学模型的建立中使用了关于网柄网柄藻运动的最新信息，与不同的试验组的相互作用提供了关于模型有效性的反馈。发展了适用于模拟偏微分方程组的计算方法。关于细胞和组织运动的知识也适用于网状网柄菌；它也可以用于其他几种情况，包括胚胎发育、伤口愈合、血管生成和免疫系统。基于细胞行为微观模型的宏观描述将显著改进大规模组织模拟，并扩大可行的微观精确模拟的范围。在这个项目中，研究人员开发了数学模型，以帮助理解盘基菌(一种细胞黏液霉菌)独立的、非相互作用的细胞中的信号转导、方向感知和运动如何促进大型细胞集合体的集体行为。细胞定向迁移在大多数生物体的早期发育和持续维持中起着至关重要的作用。单细胞生物，如细菌，通过趋化作用寻找食物并避免驱避剂，白细胞必须检测感染部位并向它们移动，以摄取细菌和细胞碎片，定向细胞迁移对胚胎发育和伤口愈合至关重要。细胞迁移也发生在许多疾病中；例如，在癌症中，它会导致侵袭和转移，细胞黏附和运动也在其中发挥重要作用。转移可能是癌症患者死亡的主要原因。更好地理解细胞运动的潜在影响是巨大的。控制运动不仅是癌症治疗的重要治疗目标，而且细胞和组织工程有望通过体内组织再生提供新的组织和组织。这项研究的成功取决于对细胞附着在天然和人造细胞外基质上的方式的了解，以及细胞与细胞相互作用的特征，这些特征最终决定了细胞如何移动、增殖和重塑为新的毛细血管或其他类型的功能组织。

Othmer and Stolarska The investigators formulate and analyze mathematical modelsfor signal transduction, direction sensing, and movement inindividual, non-interacting amoeboid cells and incorporate theindividual-based model in models for the collective motion oftissue-like cellular aggregates in which the cells interactstrongly. The cellular slime mold Dictyostelium discoideum isused as the model system because it exemplifies both thefree-ranging movement of individual cells and the collectivemotion of aggregates, and because it is widely used as a modelexperimental system for the study of cell movement. Currentinformation on movement of Dictyostelium is used in theformulation of the mathematical models, and interaction withdifferent experimental groups provides feedback on the validityof the models. Suitable computational techniques to simulate theresulting partial differential equations are developed. What islearned about cell and tissue movement is applicable toDictyostelium; it can be used in several other contexts,including embryonic development, wound healing, angiogenesis, andthe immune system. Macroscopic descriptions based on microscopicmodels of cell behavior will significantly improve large-scaletissue simulations and expand the scope of feasible,microscopically-accurate simulations. In this project the investigators develop mathematicalmodels to help understand how signal transduction, directionsensing, and movement in individual, non-interacting cells ofDictyostelium discoideum, a cellular slime mold, contribute tothe collective behavior of large aggregates of cells. Directedcell migration plays an essential role in the early developmentand ongoing maintenance of most organisms. Single-cell organismssuch as bacteria find food and avoid repellents by chemotaxis,leukocytes must detect sites of infection and move toward them inorder to ingest bacteria and cellular debris, and directed cellmigration is essential for embryonic development and woundhealing. Cell migration also occurs in many diseases; in cancer,for instance, it leads to invasion and metastasis, and celladhesion and motility also have important roles there. Metastasisis probably the major cause of death in cancer patients. Thepotential impact of a better understanding of cell motion isenormous. Not only is control of motility an importanttherapeutic target for cancer treatment, but cell and tissueengineering holds the promise to provide new tissues and organsby in vivo tissue regeneration. The success of this hinges onunderstanding the ways that cells attach to natural andartificial extracellular matrix, as well as the characteristicsof the cell-cell interactions that eventually dictate how cellsmove, proliferate and remodel into new capillaries or other typesof functional tissues.