Molecular dynamics and force generation: shedding new light on cell mechanosensing and communication

Living tissues are more than packed cells. In fact, much of a tissue's volume is made up of extracellular space, filled with a complex meshwork of sugars, water, minerals and proteins called the extracellular matrix (ECM). Cells contain special structures called focal adhesions, the ‘fingers’ of the cell, which probe the surrounding matrix and neighboring cells. Depending on what they feel, cells will adapt their shape, size and structure in response to mechanical stimuli. Mechanically induced signals are important for the function and development of every cell. In this project we will develop new tools to study how cells sense and react to the physical forces and properties of the surrounding matrix; and how these signals are communicated to other cells. We will use synthetic materials that mimic the natural cellular environment, label proteins involved in force-sensing mechanisms and use small molecular springs in cell adhesions or linked to the skeleton of the cell to measure the tension generated in these structures. By combining these materials and probes with advanced microscopic methods, we will be able to ‘see’ how the matrix controls cellular behavior, how mechanical properties are sensed and transmitted, at a molecular level. The knowledge of how forces control the collective behavior of cells will have an impact on a wide range of scientific disciplines, for instance, in the fields of tissue engineering and cardiovascular diseases.