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Nanopatterned Surfaces to Control Cell Fate

控制细胞命运的纳米图案表面

基本信息

批准号：
7140186
负责人：
KEVIN Edward HEALY
金额：
$ 16.78万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-06 至 2007-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7140186
关键词：
biomaterial interface interaction cell adhesion cell differentiation cell growth regulation cell membrane cell morphology cell proliferation membrane activity nanotechnology surface property

项目摘要

DESCRIPTION (provided by applicant): Cell morphology has a profound effect on a range of cellular events, such as proliferation, differentiation, cytoskeletal organization, and presumably gene expression. One proposed mechanism for the transduction of cell shape information into gene expression is through mechanical forces transmitted via the direct link of the cytoskeleton to the nucleus, and in particular to nuclear matrix proteins (NMPs) such as NMP 1 and 2. Previously, we have developed methods for both controlling cell and nuclear shape on the micron length scale, and measuring in situ mRNA expression in an effort to help elaborate relationships that control cell fate. Although previous studies have employed surfaces with spatially resolved chemistry to study cell shape/function relationships and their effect on protein synthesis, in situ gene expression (mRNA) and protein synthesis as a function of the cell projected area and nuclear shape, these studies have been limited by the inability to independently control the input into the cell via cell surface contacts. This limitation has prevented the analysis of the effect of ligand type, density, and nanoscale distribution in controlling cell fate. To alleviate this problem, fabrication of more elaborate surfaces are necessary to design experiments that examine surface properties that control cell fate. In this proposal we attempt to circumvent the aforementioned limitation by creating surfaces that can control peptide ligand density and ligand nanoscale distribution to control the spatial arrangements of focal adhesion on a nanometer (nm) length scale. By controlling the cytoskeleton, we anticipate that we can independently control the cell's shape and the shape of its' nucleus. We will exploit a custom built NSOM laser to "write" patterns of peptide ligands that subsequently engage with integrin receptors for precise control of focal adhesion locations on the nm length scale. These culture surfaces will have a number of conceivable applications in the fields of biotechnology, dentistry and medicine. First, because they will allow cell and nuclear shape to be controlled as an independent variable, they are invaluable as experimental platforms for the study of cell shape/gene expression hierarchies. Second, since these surfaces will enable the fundamental control of cell differentiation and proliferation, we ultimately hope to map the nanopatterning technique to the surface of biomaterials, such as dental implants to control cell behavior at the interface.

描述（由申请人提供）：细胞形态对一系列细胞事件具有深远的影响，例如增殖、分化、细胞骨架组织以及可能的基因表达。一种将细胞形状信息转导为基因表达的机制是通过细胞骨架与细胞核的直接连接传递机械力，特别是传递给核基质蛋白 (NMP)，如 NMP 1 和 2。此前，我们开发了在微米长度尺度上控制细胞和核形状的方法，并测量原位 mRNA 表达，以帮助阐明控制细胞命运的关系。尽管之前的研究已经利用具有空间分辨化学的表面来研究细胞形状/功能关系及其对蛋白质合成、原位基因表达（mRNA）和蛋白质合成作为细胞投影面积和核形状的函数的影响，但这些研究由于无法通过细胞表面接触独立控制进入细胞的输入而受到限制。这种限制阻碍了对配体类型、密度和纳米级分布在控制细胞命运中的影响的分析。为了缓解这个问题，需要制造更精细的表面来设计实验来检查控制细胞命运的表面特性。在本提案中，我们试图通过创建可以控制肽配体密度和配体纳米级分布的表面来规避上述限制，以控制纳米（nm）长度尺度上粘着斑的空间排列。通过控制细胞骨架，我们预计可以独立控制细胞的形状及其细胞核的形状。我们将利用定制的 NSOM 激光器来“写入”肽配体的模式，随后与整合素受体结合，以在纳米长度范围内精确控制粘着斑位置。这些培养表面将在生物技术、牙科和医学领域有许多可想象的应用。首先，因为它们允许将细胞和核形状作为自变量进行控制，所以它们作为研究细胞形状/基因表达层次结构的实验平台是非常宝贵的。其次，由于这些表面将能够从根本上控制细胞分化和增殖，因此我们最终希望将纳米图案化技术映射到生物材料的表面，例如牙种植体，以控制界面处的细胞行为。