What does a cell know about its environment? It gathers chemical information with the help of receptors and channels in the cell membrane. That is how a cell in the pancreas, for example, knows if the there is too much sugar in the blood and thus whether insulin needs to be produced. But a cell requires more than just chemical information – it also needs to detect the mechanical properties of its environment. That way the cell can determine, for example, whether there is an opening that it can slip through. Recent results show that stem cells use such mechanical information to determine which cell type (for example bone cell, brain cell, or muscle cell) they will differentiate into. What remains unclear is what the cell uses as a 'sense' to determine external mechanical characteristics.
Molecules on the boundary
FOM PhD student Elizaveta Novikova (Eindhoven University of Technology), working in this FOM programme, is searching for the answer at the boundary between the cell and the outside world. Proteins called integrins, situated at this boundary, directly link the cell skeleton to the world around it. Recent experiments demonstrate that some integrins form catch bonds: bonds that become stronger when stressed. As these proteins are directly sensitive to mechanical signals, Novikova suspected they might play a role in mechanical sensing. She developed a model that captures both the characteristics of single catch bonds and the collective behaviour of large clusters of catch bonds. Her calculations reveal that as the environment gets stiffer, the number of bound catch bonds increases in accord.
The cell thus has something very useful at its disposal. An internally measurable quantity – the number of attached integrin catch bonds – is a direct measure for the mechanical stiffness of the external environment. Novikova therefore proposes that a first and crucial step for mechanosensing takes place right there, in integrin clusters at the molecular level.
This insight provides new handles to control or program cellular response by manipulating the external environment. An appropriately designed environment can, conceivably, guide the movement of cells in predetermined directions, or force stem cells to differentiate into a specific cell type.