Mathematical Modeling and Computational Analysis of Cell and Tissue Movement

细胞和组织运动的数学建模和计算分析

• 批准号: 0317372
• 负责人: Hans Othmer
• 金额: $ 18万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2006-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0317372&HistoricalAwards=false
• 关键词: Mathematical; Modeling; Computational; Analysis; Cell

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.

奥特默和斯托拉斯卡 研究人员制定和分析数学模型的信号转导，方向感测，和运动在个人，非相互作用的变形虫细胞，并纳入基于个人的模型集体运动的组织样细胞聚集体中的细胞相互作用强烈的模型。 细胞黏菌Dictyosteelium discoideum被用作模型系统，因为它既能体现单个细胞的自由运动，又能体现聚集体的集体情感，而且它被广泛用作研究细胞运动的模型实验系统。 目前的信息Dictyosteoblasts的运动被用于制定的数学模型，和互动与不同的实验组提供反馈的validityof模型。 适当的计算技术来模拟所产生的偏微分方程。 我们对细胞和组织运动的了解也适用于网骨藻;它还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善大规模组织模拟，并扩大可行的微观精确模拟的范围。 在这个项目中，研究人员开发了一个细胞模型，以帮助理解细胞黏菌Dictyostebellum discoideum的单个非相互作用细胞中的信号转导、方向感测和运动如何促成细胞大聚集体的集体行为。 定向细胞迁移在大多数生物的早期发育和持续维持中起着重要作用。 单细胞生物如细菌通过趋化性寻找食物并避开驱虫剂，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，它导致侵袭和转移，细胞粘附和运动也在那里发挥重要作用。 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。 不仅是运动的控制癌症治疗的一个重要的治疗目标，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器官。 这一研究的成功取决于对细胞附着于天然和人工细胞外基质的方式的理解，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、增殖和重塑成新的毛细血管或其他类型的功能组织。