The mechanical properties of structural animal tissues like bone, tendon and skin are determined by the extracellular matrix (ECM) of the tissue, a complex, changeable 3D material that forms a scaffold around the tissue’s cells. Cells in the tissue change the ECM molecular structure in response to mechanical stresses on it, to toughen or repair it, for example. Structural tissues are subject to constant macroscopic strains from everyday movement and from cells in the tissue exerting traction forces. Inevitably, the matrix is often damaged by mechanical stresses. When this happens, cells repair the damage. The damage may be considerable, for example, the result of sudden high tensile stress on the tissue, or it may be repeated low-grade damage. The cell response to these two situations needs to be very different: full scale removal of damaged material and new matrix constructed in the former case; adding strengthening material in the latter to prevent the damage from occurring again. The principle of ECM adaption here is behind the loss of bone mass in space flight, for instance. The ECM is a complex 3D architecture of solid proteins and sugars. Drivers for cell behaviour are encoded into its detailed chemical structures. They are communicated to cells through highly specific molecular binding interactions between those chemical structures and proteins in the cell’s outer membrane. For cells to respond appropriately when they alter the ECM structure after mechanical stress or damage, they need to detect the mechanical history of the ECM. What the ECM chemical structures are that communicate the mechanical history of the ECM to cells is still poorly understood.
Recent new work has shown that chemistry happens in the ECM under mechanical strains. Covalent bonds break resulting in chemical modifications to extracellular proteins, the modifications depending on the strain. This suggests Nature has evolved an exquisite mechanism to communicate the mechanical history of the ECM to cells, using mechanochemistry resulting from the forces on the tissues to accumulate specific molecular cues into the ECM.
The challenge now is to determine what these ECM mechanochemical modifications are, how cells use them and how they change in ageing and diseases such as diabetes and cancer. In a major project funded by the European Research Council, we are developing new solid-state NMR spectroscopy and imaging methodology to advance important new insight into how cells interpret their environment that will impact on how we understand human diseases and ageing.