Regulation of epithelial and endothelial cell-cell junctions by mechanical forces

我们身体的大部分部位在机械力的作用下不断发生变化。例如，每次吸气时，我们的肺都会扩张。我们吃完东西后，肠道肌肉收缩，推动食物通过肠道。当我们移动胳膊或腿时，我们的皮肤需要伸展或压缩。我们的血管暴露在心脏产生的脉动血液中。我们的肺、肠道和皮肤上布满了上皮细胞，它们是外部环境和我们身体之间的接口。上皮细胞需要充当屏障：我们的皮肤、肺和肠道上皮细胞保护我们免受细菌、病毒以及有毒物质的侵害。我们的血管被称为内皮细胞的细胞排列，它们调节血液中营养物质的运输，供应给我们所有的组织和器官。内皮细胞也需要形成一个屏障来阻止血液泄漏到我们的组织中，但仍然允许白细胞进入组织来对抗感染和修复伤口。上皮细胞和内皮细胞通常彼此紧密相连，形成一个密封的屏障，类似于魔术贴。尽管上皮细胞和内皮细胞不断暴露在快速变化的机械力下，但重要的是它们足够灵活，既能移动，又能保持其屏障功能。此外，随着婴儿逐渐成长为成年人，这些细胞需要分裂，但仍然形成紧密的屏障。此外，如果它们暴露在持续变化的机械力下，比如血压升高，细胞需要适应这种变化。在我们的研究中，我们的目标是找出上皮细胞和内皮细胞如何适应机械力的变化。我们将重点研究邻近的上皮细胞或内皮细胞如何通过其类似魔术贴的附着物将机械力的信息传递给彼此。细胞之间的这些附着物包含数千种不同类型的分子。我们将测试这些分子中哪些对于检测来自邻近细胞的信息是重要的，以及这些分子如何适应机械力的快速变化。我们还将确定细胞是如何对机械力水平的长期变化做出反应的，也许是通过改变它们的维可牢式附着物的组成来使它们更强或更弱。上皮细胞和内皮细胞由于在我们体内的位置不同，承受着不同的机械力。我们将直接比较这两种类型的细胞中感应机械力所需的分子。这将为细胞如何适应环境和它们所经历的压力提供新的见解。通过我们的工作，我们将获得重要的信息，了解我们的身体如何通过上皮细胞，以及血液和组织之间的内皮细胞，形成和维持与外界的屏障。这将有助于开发修复或替换受损组织的新方法，例如在手术后，大面积受伤或严重感染。

Most parts of our body are constantly changing in response to mechanical forces. For example, every time we breathe in, our lungs expand. Our gut muscles contract to push food through the gut after we eat. When we move our arms or legs, our skin needs to stretch or compress. Our blood vessels are exposed to pulsatile blood flow generated by our hearts. Our lungs, gut and skin are lined by cells called epithelial cells, which provide the interface between the external environment and our body. Epithelial cells need to act as barriers: our skin, lung and gut epithelial cells protect us from bacteria and viruses, as well as toxic substances. Our blood vessels are lined by cells called endothelial cells, which mediate the transport of nutrients out of the blood stream to supply all our tissues and organs. They also allow Endothelial cells also need to form a barrier to stop the content of the blood leaking out into our tissues, yet still allow white blood cells into the tissues to fight infections and repair wounds. Epithelial cells and endothelial cells are normally tightly attached to each other to make a sealed barrier, similar to Velcro. Despite all the rapidly changing mechanical forces that epithelial cells and endothelial cells are constantly exposed to, it is important that they are flexible enough to move yet maintain their barrier functions. In addition, as a baby gradually grows into an adult, these cells need to divide yet still form tight barriers. Furthermore, if they are exposed to a sustained change in mechanical force, such as an increase in blood pressure, the cells need to adapt to this change.In our research, we aim to find out how epithelial cells and endothelial cells adapt to changes in mechanical forces. We will focus on studying how neighbouring epithelial or endothelial cells pass on messages about mechanical force to each other through their Velcro-like attachments. These attachments between cells contain thousands of different types of molecules. We will test which of these molecules are important for detecting messages from neighbouring cells, and how these molecules adapt to rapid changes in mechanical forces. We will also determine how cells respond to long-term changes to the level of mechanical forces, perhaps by altering the composition of their Velcro-like attachments to make them stronger or weaker.Epithelial cells and endothelial cells experience different kinds of mechanical forces because of their different locations in our bodies. We will directly compare the molecules that are required for sensing mechanical forces in these two types of cells. This will provide new insight into how cells adapt to their environment and the stresses that they experience. Through our work, we will generate important information about how our body forms and maintains barriers to the outside world, via epithelial cells, and between the blood and tissues, via endothelial cells. This will be useful to develop new ways to repair or replace damaged tissues, for example after operations, extensive wounding or severe infections.