Rotational constraint contributes to collective cell durotaxis

Directed cell migration following the gradients of extracellular matrix stiffness, termed durotaxis, plays an essential role in development, wound healing, and cancer invasion. Here, we develop a cytoskeleton-based mechanical model to study the migration modes of both isolated cells and cell clusters on gradient substrates. We find that collective cell durotaxis is attributed to the geometrical restriction of cell rotation by neighboring cells, leading to a different migration mode from isolated cells. Moreover, isolated cells are able to undergo directed migration on a soft substrate with relatively high stiffness gradients. In addition, collective cell durotaxis is far more efficient than single-cell durotaxis. The migration mode is determined by the competition between the difference of traction forces between the cell-substrate interface and the random force from microenvironments. This study indicates that isolated cells are more sensitive to environmental fluctuations, whereas cell clusters can counteract the effects of fluctuations by cell-cell interactions.