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

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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.