Probing the mechano-biology of cell-cell adhesion in a novel single cell assay

在新型单细胞测定中探讨细胞间粘附的力学生物学

• 批准号: EP/Y002245/1
• 负责人: Darius Koester
• 金额: $ 21.07万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY002245%2F1
• 关键词: Probing; mechano; biology; cell; adhesion

We, animals and many other organisms are built from lots of cells. These are not simple building blocks that are passively stuck together, but each cell contains an elaborate machinery to connect to its neighbours and exert force on one other. This crucial ability is provided by multiple adhesion molecules at the cell surface that link up to the force generating cytoskeleton via adapter proteins. The balancing of forces and how strong different cells stick to each other are all important cues in the orchestration of cell motion and differentiation during development. And it is now clear that mechanical changes on the cellular level can alter the fate of the tissue. In cancer, the detachment of cells leading to metastasis is related to a change of cell mechanics.We are interested to dissect the basis of intracellular mechanical signalling in cell-cell adhesion. For this, we are establishing a new international collaboration to study the role of forces in the process of cell adhesion. We use novel assay to look at the cell-cell adhesion interface with high resolution fluorescence microscopy by replacing one cell with a planar lipid bilayer containing adhesion molecules. This will be combined with three modes of mechanical manipulations: confinement, shear stress and lateral stretch. In addition to fluorescence microscopy techniques to follow the dynamics of adhesion and cytoskeletal proteins, we will employ interferometric reflection microscopy to reveal the fluctuations of the cell membrane with nanometre precision. This will give us an unprecedented insight into the protein dynamics and cell membrane mechanics during cell adhesion. The tools for such experiments are often built by individual labs which limits the range of people having access to such equipment. That's why we want to use the combined expertise of this collaboration to design and engineer MechanoWOSM, an open source microscope platform for mechano-biology experiments.

我们，动物和许多其他生物都是由许多细胞建造的。这些不是一个简单的构建块，它们被动地粘在一起，但是每个单元都包含一个精美的机械，可以连接到其邻居并互相施加力。这种关键能力由细胞表面的多个粘附分子提供，该细胞表面与通过衔接蛋白产生细胞骨架的力联系在一起。力的平衡以及强大的不同细胞彼此之间的依存方式都是在发育过程中细胞运动和分化的编排中的重要提示。现在很明显，细胞水平上的机械变化可以改变组织的命运。在癌症中，导致转移的细胞脱离与细胞力学的变化有关。我们有兴趣剖析细胞细胞粘附中细胞内机械信号的基础。为此，我们正在建立一种新的国际合作，以研究力在细胞粘附过程中的作用。我们使用新颖的测定方法来查看具有高分辨率荧光显微镜的细胞细胞粘附界面，通过用一个含有粘附分子的平面脂质双层代替一个细胞。这将与三种机械操作模式结合在一起：限制，剪切应力和侧面拉伸。除荧光显微镜技术遵循粘附和细胞骨架蛋白的动力学外，我们还将采用干涉反射显微镜以揭示具有纳米精度的细胞膜波动。这将使我们对细胞粘附过程中的蛋白质动力学和细胞膜力学有前所未有的见解。这种实验的工具通常是由个别实验室构建的，这些实验室限制了使用此类设备的人的范围。这就是为什么我们希望将这种合作的联合专业知识用于设计和工程师Mechanowosm，这是一个用于机械生物学实验的开源显微镜平台。