Metastases occur when tumour cells detach from the primary tumour and migrate to distant sites through the connective tissue of organs. During this migration process, the tumour cells generate mechanical forces in order to overcome the resistance of the connective tissue or to change their shape so they can pass through very small pores. We have developed a method for measuring the mechanical forces of tumour cell as they migrate through artificial connective tissue made of collagen, which mimics the natural matrix of organs in terms of its chemical composition, structure and other material properties. The idea behind the method is simple: we first measure the deformation of the connective tissue around the migrating cells. If the elasticity of the connective tissue is known, it can then be used like a spring scale to calculate the cell forces from the tissue deformations.
A particular challenge was that connective tissue is initially soft when forces are weak, but stiffens at the level of forces generated by tumour cells. Tumour cells also use part of their forces to elongate into a spindle-like shape, allowing them to migrate at a remarkable speed even through very small pores of the connective tissue. In a next step, we will apply this method to investigate differences in the cell forces between differently aggressive tumours.
Read the full publication in Nature Methods.