Biology of cell-surface interactions

细胞表面相互作用的生物学

• 批准号: 355615-2009
• 负责人: Hamilton, Douglas
• 金额: $ 2.61万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=498127
• 关键词: Biology; cell; surface; interactions

In organs and tissues of the human body, cells adhere to a complex scaffold-like protein mesh called the extracellular matrix (ECM). The ECM provides cells with many stimuli and signals that cells need to behave normally. However, sometimes cells are forced to come into contact with artificial materials. Central in many bioengineering applications is the attachment of human cells to artificial materials, but the factors important in successful cell-material attachment are not well understood. Our previous research has identified that the topography and chemistry of materials can be altered to enhance cell attachment. When a cell attaches to a surface, it results in activation of important signaling molecules required by the cells to survive. Cells attach to surfaces through specialized sites called focal adhesions (FA), and research is highlighting that these adhesions are very important sites in cells. FAs are responsible for relaying the attachment event to other areas within the cells that control normal cell behaviour. We hypothesize that by altering the chemistry and topography of the materials, we can enhance the function of human fibroblasts. Using techniques harnessed from the microelectronic industry, it has become possible to produce structures with precisely defined surfaces for cell-biological studies, thus allowing the reaction of cells to defined topographic and chemical features to be observed. The aim of our research is 1) to investigate the interactions of human fibroblasts with nano- and micro-metric repeating groove topographies, 2) to quantify matrix assembly and tissue development by fibroblasts on nano- and micro-metric repeating groove topographies. The results of the study will directly address how cells transmit external stimuli into signals that regulate their normal behaviour, which will be important for all areas of cell biology. We anticipate that the information produced by our program could in the long term be used in cell and tissue engineering applications, where our lack of understanding of cell-material interactions are limiting the development of engineered tissue substitutes.

在人体的器官和组织中，细胞粘附于称为细胞外基质（ECM）的复杂支架样蛋白质网。ECM为细胞提供细胞正常行为所需的许多刺激和信号。然而，有时细胞被迫与人造材料接触。许多生物工程应用的中心是将人类细胞附着到人工材料上，但对成功的细胞-材料附着的重要因素还没有很好的了解。我们以前的研究已经确定，可以改变材料的形貌和化学性质以增强细胞附着。当细胞附着在表面上时，它会激活细胞生存所需的重要信号分子。细胞通过称为粘着斑（FA）的专门位点附着在表面上，研究强调这些粘着斑是细胞中非常重要的位点。FA负责将附着事件中继到细胞内控制正常细胞行为的其他区域。我们假设，通过改变材料的化学性质和形貌，我们可以增强人成纤维细胞的功能。利用微电子工业的技术，已经可以生产具有精确限定的表面的结构用于细胞生物学研究，从而允许观察细胞对限定的地形和化学特征的反应。我们的研究目的是1）研究人成纤维细胞与纳米和微米重复凹槽形貌的相互作用，2）量化成纤维细胞在纳米和微米重复凹槽形貌上的基质组装和组织发育。这项研究的结果将直接解决细胞如何将外部刺激转化为调节其正常行为的信号，这对细胞生物学的所有领域都很重要。我们预计，我们的计划产生的信息可以在长期内用于细胞和组织工程应用，我们缺乏对细胞-材料相互作用的理解限制了工程组织替代品的发展。