Mechanisms of Monolayer Migration

描述(由申请人提供)：这个小项目将在经典的划痕创伤试验中完成基于代理的多细胞迁移计算模型的测试和开发。该模型试图模拟没有自由参数的简单永生细胞类型(3T3-L1成纤维细胞)的实验。使用L1细胞是因为这些细胞在反复传代时表现出稳定的生长和迁移特性，并以稳定的集体方式重复愈合伤口，尽管它们缺乏特殊的粘连连接。集体迁移发生在各种重要的医学环境中，包括伤口愈合、血管生成和某些癌症的转移。因此，对L1系统中集体迁移机制的定量理解应该为解释和/或调节更复杂的细胞类型的行为提供一个基线。为了实现预测模型，该项目将通过两个目标相继进行。早期的努力将集中在建造一种专门的多相干涉显微镜，用于在伤口愈合实验期间实时测量细胞高度。细胞高度的测量是必要的，因为现有的模型预测，一旦细胞完全铺展在基质上，集体迁移到细胞分散的分解就会发生。剩下的工作将测试当前计算模型的这一预测和其他预测，测量缺失的参数，并改进模型，以得出基本细胞类型的单层迁移的明显预测模型。公共卫生相关性：该项目将开发一个集体细胞迁移的预测性计算模型。由于集体细胞迁移是组织修复和发育的基础，该模型可以作为再生和抗肿瘤疗法以及组织工程表面的基本设计平台。

DESCRIPTION (provided by applicant): This small project will complete testing and development of an agent-based computational model of multi-cell migration in the classic scratch wound assay. The model attempts to mimic experiments on a simple immortal cell type (3T3-L1 fibroblasts) without free parameters. L1 cells are used because these cells exhibit stable growth and migration characteristics upon repeated passages, and reproducibly heal wounds in a steady, collective fashion despite their lack of specialized adhesive junctions. Collective migration occurs in a variety of medically important circumstances including wound healing, angiogenesis, and metastasis by some cancers. Thus the development of a quantitative understanding of the mechanisms of collective migration in the L1 system should provide a baseline for interpreting and/or modulating the behavior of more complex cell types. To achieve a predictive model the project will proceed successively through two aims. Early efforts will focus on the construction of a specialized multiphase interference microscope for the real-time measurement of cell height during wound healing experiments. Cell height measurements are needed because the existing model predicts that the breakdown of collective migration into cell scatter occurs once cells become fully spread on the substrate. The remaining efforts will test this and other predictions of the current computational model, measure missing parameters, and refine the model to arrive at a demonstrably predictive model of monolayer migration for a basic cell type. PUBLIC HEALTH RELEVANCE: This project will develop a predictive computational model of collective cell migration. Because collective cell migration is fundamental in tissue repair and development, the model can serve as a platform for rationale design of regenerative and anti-tumor therapies and tissue-engineered surfaces.