THE ROLE OF ECM MECHANICS IN REGULATING CAPILLARY MORPHOGENESIS

ECM 力学在调节毛细血管形态发生中的作用

• 批准号: 8362700
• 负责人: Andrew J Putnam
• 金额: $ 0.31万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362700
• 关键词: 3-Dimensional; Adhesions; Biotechnology; Blood capillaries; Cell physiology; Cells; Cues; D Cells; Ethylene Glycols; Extracellular Matrix; Fibrinogen; Funding; Grant; Hybrids; Hydrogels; Lasers; Ligands; Measurement; Measures; Mechanics; Methodology; Methods; Molecular; Morphogenesis; National Center for Research Resources; Phenotype; Principal Investigator; Property; Research; Research Infrastructure; Research Personnel; Resources; Role; Source; System; United States National Institutes of Health; base; capillary; cell motility; cost; density; ethylene glycol; novel; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The importance of ECM mechanics on 2-D cell responses (e.g., adhesion, spreading, motility, proliferation, and even differentiation) is widely recognized and well characterized. However, the effects of intrinsic mechanical cues on longer-term phenotypic responses of cells in 3-D culture remain undefined, as do the molecular mechanisms underlying these phenotypic changes. Efforts to relate changes in cell phenotype with substrate mechanics in 3-D have been hindered in part by the lack of suitable material systems. Ideally, a suitable material system should provide the means to predictably tune substrate mechanical properties independently from adhesion ligand density and proteolytic sensitivity. In addition to material limitations, efforts to dissect the influence of ECM mechanics on cell function in 3-D have been hampered by the lack of suitable methods to assess mechanical properties at the local cell-material interface. Most researchers have instead chosen to utilize bulk measurements of a material's elastic and viscoelastic properties and to correlate these with cell function; unfortunately, these do not adequately depict the local microenvironment. We proposed to utilize a unique biosynthetic hybrid hydrogel based on poly(ethylene glycol) and fibrinogen. Furthermore, we proposed to develop novel methodologies to measure the local mechanical properties this material. The following three specific aims constitute the proposed study.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 ECM力学对2-D细胞反应的重要性（例如，粘附，扩散，运动，增殖甚至分化）是广泛认识和表征的。然而，内在的机械提示对3-D培养物细胞长期表型反应的影响仍然不确定，这些表型变化的分子机制也是不确定的。将细胞表型变化与3-D中的底物力学变化相关联的努力部分受到缺乏合适的材料系统的一部分。理想情况下，合适的材料系统应为可预测的底物机械性能提供手段，而不是与粘附配体密度和蛋白水解敏感性独立的。除了材料局限性外，缺乏评估局部细胞材料界面上的机械性能的方法，也阻碍了剖析ECM力学对3D细胞功能的影响的努力。 相反，大多数研究人员选择利用材料弹性和粘弹性特性的大量测量，并将其与细胞功能相关。不幸的是，这些并不能充分描绘当地的微环境。我们提议利用基于聚乙二醇和纤维蛋白原的独特生物合成杂化水凝胶。 此外，我们建议开发新的方法来测量该材料的局部机械性能。以下三个特定目标构成了拟议的研究。