Cell adhesion mediated self-recognition

细胞粘附介导的自我识别

基本信息

批准号：
8325079
负责人：
Soichiro Yamada
金额：
$ 29.06万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2014-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Cell-cell adhesion is a fundamental feature of multi-cellular systems. The goal of this proposal is to analyze how individual epithelial cells recognize neighboring cells to form mutual cell-cell adhesion while rejecting self-contact. Homophilic adhesive receptors on two opposing cells rapidly bind to form a cell-cell adhesion, yet the same receptors on two thin protrusions originating from the same cell surface do not. This self-awareness of individual cells suggests that cells can distinguish the chemically identical surface of neighboring cells from their own. We hypothesize that the self-recognition mechanism is mechanically regulated, and that the cadherin complex is a mechano-sensing complex that detects external forces, thereby providing a signaling cue for mutual cell adhesion. In the absence of external forces, the mechano-signal is off, and leads to the elimination of self-contacts. Using innovative micro-fabricated substrates to control self-contacting events, we will analyze the formation of self-contacts and the subsequent elimination of self-contacting sites. Furthermore, we have developed miniature force sensors to detect forces at the adhesive contacts and directly test our hypothesis. Our findings will also highlight how mutual cell-cell adhesion forms between neighboring cells. Once we understand the fundamental processes of self and other recognition by cells, our goal is to develop therapeutic agents that alter cell- cell adhesion and can be used to prevent cancer cell invasion or pathogen infection. PUBLIC HEALTH RELEVANCE: Regulation of cell-cell adhesion plays critical roles in development and homeostasis of multi-cellular organisms. The goal of this proposal is to analyze how individual epithelial cells recognize neighboring cells to form mutual cell-cell adhesions while rejecting self-contact. One potential outcome of the proposed research will be the development of advanced therapeutic agents that prevent cancer cell invasion or pathogen infection.

描述（由申请人提供）：细胞细胞粘附是多细胞系统的基本特征。该提案的目的是分析单个上皮细胞如何识别相邻细胞在拒绝自我接触的同时形成相互细胞粘附的相邻细胞。两个相对细胞上的同粒子粘附受体迅速结合以形成细胞细胞粘附，但在两个源自同一细胞表面的薄突起上的同一受体却没有。单个细胞的这种自我意识表明，细胞可以将相邻细胞的化学表面与自己的化学表面区分开。我们假设自我识别机制是机械调节的，并且钙粘蛋白复合物是一种检测外部力的机械感应复合物，从而为相互细胞粘附提供了信号提示。在没有外部力量的情况下，机械信号是关闭的，导致消除自我接触。使用创新的微型制造底物来控制自我接触事件，我们将分析自我接触的形成和随后消除自我接触位点。此外，我们开发了微型力传感器来检测在粘合剂接触处的力并直接检验我们的假设。我们的发现还将突出相邻细胞之间如何形成相互细胞 - 细胞粘附。一旦我们了解了细胞的自我和其他识别的基本过程，我们的目标就是开发改变细胞粘附的治疗剂，并可用于防止癌细胞侵袭或病原体感染。公共卫生相关性：细胞细胞粘附的调节在多细胞生物的开发和体内稳态中起关键作用。该提案的目的是分析单个上皮细胞如何识别相邻细胞在拒绝自我接触的同时形成相互细胞粘附的相邻细胞。拟议研究的一个潜在结果将是开发预防癌细胞侵袭或病原体感染的晚期治疗剂。