Biology of cell-surface interactions

在人体的器官和组织中，细胞附着在一种名为细胞外基质(ECM)的复杂的支架状蛋白质网上。细胞外基质为细胞提供了许多刺激和信号，细胞需要这些刺激和信号才能正常运行。然而，有时细胞被迫与人造材料接触。在许多生物工程应用中，核心是将人类细胞附着到人造材料上，但成功的细胞-材料附着的重要因素还没有被很好地了解。我们之前的研究已经证实，材料的形貌和化学成分可以通过改变来增强细胞的附着。当细胞附着在表面时，它会激活细胞生存所需的重要信号分子。细胞通过称为焦点粘连(FA)的特殊位置附着到表面，研究强调这些粘连在细胞中是非常重要的位置。Fas负责将附着事件传递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，已经有可能制造出具有精确定义的表面的结构，用于细胞生物学研究，从而允许观察细胞对定义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沟形态的相互作用；2)定量研究成纤维细胞在纳米和微米重复沟形态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将是重要的。我们预计，从长远来看，我们的计划产生的信息可以用于细胞和组织工程应用，在这些应用中，我们对细胞-材料相互作用的缺乏正在限制组织工程化替代品的开发。

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.