Electromechanical control of cell adhesion and motility

细胞粘附和运动的机电控制

基本信息

批准号：
6928013
负责人：
MICHAEL CHO
金额：
$ 23.05万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-01 至 2007-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Tissue engineering is a relatively new but rapidly expanding field of biomedical engineering research. Because cell adhesion and motility are two critical factors in determining tissue integrity and function, elucidation and regulation of the cellular and molecular mechanisms involved in cell adhesion and motility is fundamentally important for tissue engineering. Implementation of engineered tissues in clinical applications has been successful in soft-tissue replacement or regeneration. The general use of artificial tissues is limited, however. Detailed understanding of mechanisms regulating cell adhesion and motility is expected to provide insights for controlled cell seeding, improved designing and engineering of artificial tissues. Use of non-invasive electrical stimulation (ES) offers a novel non-mechanical technique to regulate cell adhesion and motility. Projects involving the use of ES in fibroblasts, hepatocytes, and white cells and studies of lateral and rotational dynamics of membrane proteins provided an excellent basis for the proposed hypotheses in this proposal. In response to ES, the mechanotransducer integrin is likely to mediate cell adhesion and motility. Integrins redistribute on the cell surface, interact with cytoskeleton, and actively participate in dynamic formation of focal adhesion contacts. Optimized use of ES has been shown to redistribute integrins, reorganize cytoskeleton, alter calcium homeostasis, and induce guided cell migration without adversely affecting cell viability. This proposal uses unique non-invasive optical techniques, including single particle tracking and laser optical trap, to 1) track, at the single molecule level, changes in integrin motion induced by ES on the surface of human fibroblasts; 2) measure changes in the strength of integrin-cytoskeleton interactions induced by ES on controlled 2 dimensional extracellular matrices; and 3) characterize electromechanically induced and integrin-dependent cell motility in reconstituted 3 dimensional gel model. The long-term objectives of the proposed research are to manipulate and control cell adhesion and motility by the optimal use of ES and, thereby, to enhance tissue integrity and function of engineered tissues.

描述（由申请人提供）：组织工程是一个相对较新的，但生物医学工程研究的快速扩展领域。因为细胞粘附和运动性是确定组织完整性的两个关键因素和功能，阐明和调节细胞和分子细胞粘附和运动涉及的机制从根本上很重要用于组织工程。在临床中实施工程组织应用程序在软组织替代或再生方面已经成功。但是，人造组织的一般使用是有限的。详细的对调节细胞粘附和运动性的机制的理解为了提供可控细胞播种的见解，改进的设计和人造组织的工程。使用非侵入性电刺激（ES）提供了一种新型的非机械力学调节细胞粘附和运动的技术。涉及使用的项目 ES在成纤维细胞，肝细胞和白细胞中以及侧面和研究的研究膜蛋白的旋转动力学为该提议中提出的假设。为了响应ES，机械转换器整联蛋白可能介导细胞粘附和运动能力。整合素在细胞表面重新分布，与细胞骨架相互作用，并积极地参与局灶性接触的动态形成。优化的使用 ES已被证明重新分布整合素，重组细胞骨架，Alter 钙稳态，并诱导引导的细胞迁移而无需不利影响细胞活力。该建议使用独特的非侵入性光学技术，包括单个粒子跟踪和激光光学陷阱，至1）轨道，在单分子水平上，ES诱导的整联蛋白运动的变化在人成纤维细胞表面； 2）衡量强度的变化 ES在受控的2维细胞外矩阵； 3）特征是机电诱导的，并且重构3维凝胶模型中的整联蛋白依赖性细胞运动。这拟议研究的长期目标是操纵和控制通过ES的最佳使用，从而增强细胞粘附和运动性组织完整性和工程组织的功能。