Extracellular Matrix Remodeling and Tissue Mechanics

细胞外基质重塑和组织力学

基本信息

批准号：
6787193
负责人：
Denise C Hocking
金额：
$ 23.63万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-10 至 2006-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Tissue development and function depend upon a complex and dynamic interplay between cells and their surrounding extracellular matrix. Adhesion of cells to extracellular matrix proteins via specific cell surface receptors initiates intracellular signaling events that regulate many key aspects of cell behavior. Moreover, the precise composition and organization of the extracellular matrix contribute to the mechanical and permeability properties of the skin, vasculature, lungs, and other organs. In particular, the mechanical properties of load-bearing tissues, including blood vessels and cardiac muscle, are critical to their performance in the body. Hence, successful approaches to tissue engineering require not only an understanding of how cells interact with and organize extracellular matrix proteins into a complex, three-dimensional structure, but also an understanding of how these events subsequently contribute to the mechanical properties of artificial tissue constructs. Both the actin cytoskeleton and the extracellular matrix contribute quantitatively to the mechanical properties of artificial tissues. Our data indicate that the polymerization of fibronectin into the extracellular matrix plays a unique role in regulating both cytoskeletal tension generation and extracellular matrix organization. Our preliminary studies also indicate that the addition of fibronectin to cell-populated collagen lattices increases the toughness and ultimate strength of these biogels. In this proposal, we will determine how the polymerization and subsequent stabilization of fibronectin into the extracellular matrix contributes to the tensile mechanical properties of an established tissue model. Quantitatively determining how matrix fibronectin affects the tensile properties of collagen-based biogels will provide essential information that ultimately may be used to molecularly tailor extracellular matrices to enhance the performance of load-bearing tissue constructs.

描述（由申请人提供）：组织的发育和功能取决于细胞及其周围细胞外基质之间的复杂而动态的相互作用。细胞对细胞外基质蛋白的粘附通过特定的细胞表面受体引发的细胞内信号传导事件，这些事件调节细胞行为的许多关键方面。此外，细胞外基质的精确组成和组织有助于皮肤，脉管系统，肺部和其他器官的机械和渗透率。特别是，包括血管和心肌在内的承重组织的机械性能对于它们在体内的表现至关重要。因此，成功的组织工程方法不仅需要了解细胞如何与细胞相互作用并将细胞外基质蛋白组织成复杂的三维结构，还需要了解这些事件随后如何有助于人造组织结构的机械性能。肌动蛋白的细胞骨架和细胞外基质都在定量地有助于人造组织的机械性能。我们的数据表明，纤连蛋白在细胞外基质中的聚合在调节细胞骨架张力产生和细胞外基质组织中起着独特的作用。我们的初步研究还表明，将纤连蛋白添加到细胞填充的胶原蛋白晶格中增加了这些沼气的韧性和最终强度。在此提案中，我们将确定纤连蛋白在细胞外基质中的聚合和后续稳定如何有助于已建立的组织模型的拉伸机械性能。定量确定基质纤连蛋白如何影响基于胶原蛋白的沼气的拉伸特性将提供必要的信息，这些信息最终可用于分子量身定制细胞外矩阵，以增强负载载荷组织构建体的性能。