Functional proteomics of cellular mechanosensing mechanisms.

Mechanosensing enables cells to coordinate their phenotype with the mechanical properties of their tissue microenvironment. In this process, cells probe their surroundings by applying contractile forces, which produces different amounts of mechanical strain within the cells as a function of the stiffness of their extracellular substrates. Tension within cells can then affect the structure and composition of most cellular organelles, including cell adhesions, the cytoskeleton, the plasma membrane and the nucleus. On a molecular level, the conformations, modifications, interactions, and subcellular localizations of proteins have been shown to be altered by biomechanical forces. Functional proteomics aims at the analysis of these effects in a proteome wide, unbiased and high throughput manner. Emerging methods, such as crosslinking mass spectrometry and advanced protein correlation profiling, will enable future analysis of mechanosensing on the level of protein interactions in situ, and subcellular protein localization, which can now be determined with very high accuracy from whole cell analysis for thousands of proteins at once. Combined use of these mass spectrometry toolsets with the analysis of posttranslational modifications will ultimately move the field to a comprehensive list of molecular alterations in cellular mechanosensing. We will give an overview on current developments in functional proteomics and the latest applications on questions related to mechanobiology.