Mechanisms of Monolayer Migration

描述（由申请人提供）：这个小项目将在经典的抓伤实验中完成基于agent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不死细胞类型（3T3-L1成纤维细胞）的实验。之所以使用L1细胞，是因为这些细胞在反复传代后表现出稳定的生长和迁移特性，尽管缺乏专门的粘附连接，但它们仍能以稳定的集体方式愈合伤口。集体迁移发生在各种医学上重要的情况下，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的发展应该为解释和/或调节更复杂细胞类型的行为提供基线。为了实现预测模型，项目将通过两个目标依次进行。早期的工作将集中在建造一个专门的多相干涉显微镜，用于在伤口愈合实验中实时测量细胞高度。细胞高度测量是必要的，因为现有的模型预测，一旦细胞完全扩散到基质上，就会发生集体迁移到细胞分散的分解。接下来的工作将测试这一预测和当前计算模型的其他预测，测量缺失的参数，并改进模型，以得出一个基本细胞类型的单层迁移的可论证的预测模型。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.