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Mathematical investigation into the role of cell-cell communication pathways on collective cell migration

细胞间通讯途径对集体细胞迁移作用的数学研究

基本信息

批准号：
EP/K033689/1
负责人：
Raluca Eftimie
金额：
$ 12.04万
依托单位：
University of Dundee
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FK033689%2F1
关键词：
Mathematical investigation into role cell

项目摘要

A large number of fundamental processes in development and various diseases (e.g., cancer growth and invasion, wound healing, morphogenesis) are the result of the coordinated movement of cells. Independent of cell types, collective movement usually involves three factors: cell-cell and cell-matrix interactions, polarization of cells into "leaders" and "followers", and chemical and physical signals that allow cells to communicate with each other. There are multiple ways of cell movement, ranging from single cell movement to collective movement (where cells stay connected as they move).The movement of single cells has been investigated quite in detail over the past decades, and the key aspects of single cell movement (e.g., molecular control of cell protrusions, interactions between cells and their substrate) have been already identified. However, the collective movement of cells is less understood, and there are many open questions regarding the mechanisms involved in this type of movement. For example, it is less understood how cell movement and cell-cell communication interact to create new tissues, or to allow cells to colonise specific areas. Another aspect less understood is how cells interpret and integrate signals from the environment and from other cells to produce specific types of cell aggregations and collective movement. Finally, it is still unknown whether all cells sense guidance signals, or only the leader cells sense these signals and then instruct other cells to follow them.To formulate hypotheses that could help address these questions, we will derive a class of mechanistic mathematical models that describe cell movement and cell-cell interactions via different communication mechanisms. Using various mathematical techniques (e.g. travelling wave analysis, bifurcation analysis), we will investigate the role of different cell-cell communication mechanisms on the movement and structure of cell aggregations. We will also investigate the effect of parameters on the transitions between different types of cell movement behaviours.

发育中的大量基本过程和各种疾病（例如，癌症生长和侵袭、伤口愈合、形态发生）是细胞协调运动的结果。与细胞类型无关，集体运动通常涉及三个因素：细胞与细胞和细胞与基质的相互作用，细胞分化为“领导者”和“追随者”，以及允许细胞相互交流的化学和物理信号。细胞运动有多种方式，从单个细胞运动到集体运动（细胞在运动时保持连接）。在过去的几十年里，对单个细胞的运动进行了相当详细的研究，并且单个细胞运动的关键方面（例如，细胞突起的分子控制、细胞与其基质之间的相互作用）已经被确定。然而，对细胞的集体运动了解较少，并且关于这种运动所涉及的机制存在许多悬而未决的问题。例如，人们对细胞运动和细胞间通讯如何相互作用以创造新组织或允许细胞在特定区域定居的了解较少。另一个不太了解的方面是细胞如何解释和整合来自环境和其他细胞的信号，以产生特定类型的细胞聚集和集体运动。最后，目前还不清楚是所有细胞都感受到引导信号，还是只有领导细胞感受到这些信号，然后指示其他细胞跟随它们。为了制定有助于解决这些问题的假设，我们将推导出一类机械数学模型，描述细胞运动和细胞之间通过不同通讯机制的相互作用。使用各种数学技术（例如行波分析，分叉分析），我们将研究不同的细胞间通讯机制对细胞聚集体的运动和结构的作用。我们还将研究不同类型的细胞运动行为之间的过渡参数的影响。