Analysis and Engineering of Cell Function with Nanoscale Cues

利用纳米级线索分析和改造细胞功能

• 批准号: 7471159
• 负责人: Andre Levchenko
• 金额: $ 19.38万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7471159
• 关键词: Affect; Basement membrane; Binding Sites; Biochemical; Biomimetics; Caliber; Cell Polarity; Cell Shape; Cell physiology; Cells; Chemicals; Collagen; Collagen Fibril; Complex; Connective Tissue; Cues; Development; Devices; Dimensions; Endothelial Cells; Engineering; Environment; Event; Extracellular Matrix; Fibroblasts; Focal Adhesions; Generations; Growth Factor; Height; Immune response; In Vitro; Injury; Knowledge; Lead; Life; Ligands; Microfluidics; Muscle Rigidity; Nanostructures; Nanotopography; Natural regeneration; Neoplasm Metastasis; Pattern; Process; Property; Proteins; Public Health; Range; Research; Role; Running; Series; Shapes; Signal Transduction; Signal Transduction Inhibitor; Standards of Weights and Measures; Structure; Surface; Testing; Tissue Engineering; Tissues; Variant; Work; Wound Healing; cell behavior; cell motility; cell type; density; desire; extracellular; fluid flow; in vivo; migration; nano; nanometer; nanopattern; nanoscale; nanostructured; neglect; polarized cell; receptor binding; response; scaffold; size

DESCRIPTION (provided by applicant): Living tissues are intricate ensembles of cells of different types embedded in complex and well defined structures of extracellular matrix (ECM). Cell orientation and migration within tissues can be guided both by the organization of ECM and gradients of extracellular chemical ligands. Cell migration is essential for such diverse processes as tissue repair and regeneration following injury, innate immune response, cancer metastasis and various developmental events. Unfortunately, our ability to analyze cell polarization and migration is severely limited by the lack of devices capable of precise definition of the cell micro-environment, both in terms of gradients of chemical cues and nano-scale level control of the cell substratum. In this application, we propose to develop and test a series of biomimetic micro-devices combining the advantages of precise definition of both nano-topographic features and micro-scale fluid flows leading to generation of complex sets of guidance cues. We hypothesize that the combined effects of the nano-topography and spatially distributed signaling ligands will be integrated into the cell polarity and migration decisions through regulated localization (and dimensions) of focal adhesions and redistribution of the occupancy of the receptor binding sites. We anticipate that the proposed work will result in both increased understanding of the fundamental aspects of establishment of cell polarity and guidance, and allow us to establish general principles for development of more precise and defined scaffolds for tissues engineering. PUBLIC HEALTH RELEVANCE This research is aimed at understanding of how diverse cell functions are controlled by the nano-scale features of cell micro-environment. These features mimic the extracellular matrix found in the natural cell micro-environment, but can also be used to guide cell behavior in a desired manner. Therefore, the exploratory research proposed in this application will have important implications for advanced tissues engineering problems, of high potential relevance to public health.

描述（由申请人提供）：活组织是嵌入在复杂且明确的细胞外基质（ECM）结构中的不同类型细胞的复杂集合。组织内的细胞定向和迁移可以通过 ECM 的组织和细胞外化学配体的梯度来指导。细胞迁移对于损伤后的组织修复和再生、先天免疫反应、癌症转移和各种发育事件等多种过程至关重要。不幸的是，我们分析细胞极化和迁移的能力受到严重限制，因为缺乏能够精确定义细胞微环境的设备，无论是在化学线索的梯度还是细胞基质的纳米级水平控制方面。在此应用中，我们建议开发和测试一系列仿生微型设备，结合精确定义纳米地形特征和微尺度流体流动的优势，从而生成复杂的引导线索集。我们假设纳米形貌和空间分布的信号配体的综合效应将通过调节粘着斑的定位（和尺寸）和受体结合位点的占用重新分布而整合到细胞极性和迁移决策中。我们预计所提出的工作将加深对建立细胞极性和引导的基本方面的理解，并使我们能够建立开发更精确和更明确的组织工程支架的一般原则。 公共健康相关性 这项研究旨在了解细胞微环境的纳米级特征如何控制不同的细胞功能。这些特征模仿了自然细胞微环境中发现的细胞外基质，但也可用于以所需的方式引导细胞行为。因此，本申请中提出的探索性研究将对先进的组织工程问题产生重要影响，与公众健康具有高度的潜在相关性。