Just as we can feel whether we are lying on a soft blanket or hard rocks, our cells sense whether they are in a soft or rigid mechanical environment. However, the molecular mechanisms underlying cells’ ability to detect tissue stiffness are largely unknown.
Mechanical forces acting across individual molecules in cells are extremely small and cannot be measured by conventional methods. Scientists have now developed a new technique to quantify forces of only a few piconewton in cells. As a result, the researchers were able to identify the central mechanism that allows cells to sense the rigidity of their environment.
To measure the exerted molecular forces, the team engineered two novel fluorescent biosensors that change their color in response to piconewton forces. Genetic insertion of these biosensors into the protein of interest allows the microscopic evaluation of molecular tension in living cells.
By applying the method to the cell adhesion protein talin, the researchers discovered the central mechanism that allows cells to feel their mechanical environment. Cells in which talin is not able to form mechanical linkages can no longer distinguish whether they are on a rigid or a soft surface.
Th Disruption of talin’s mechanical engagement does not impair integrin activation and initial cell adhesion but prevents focal adhesion reinforcement and thus extracellular rigidity sensing. Intriguingly, talin mechanics are isoform specific so that expression of either talin-1 or talin-2 modulates extracellular rigidity sensing.
Since talins are present in all cells of our body, the researchers believe that they have found a general mechanism cells use to measure the extracellular rigidity.