Cell navigation through complex environments

Cells constantly move through tissues during processes such as development, wound healing, and cancer invasion. It is generally believed that cells migrate toward regions where they can better adhere, following chemical or mechanical “tracks” in the environment. However, using state-of-the-art microfabrication and force mapping tools, we discovered that this rule can break down under certain mechanochemical conditions.We showed that when cells move through narrow spaces—similar to those found in dense tissues—they can reverse their direction and migrate away from high-adhesion regions. Through experiments and modelling, the study demonstrates that physical confinement alters the organization of the cell cytoskeleton and shifts the balance of forces required for movement.This finding challenges long-standing assumptions about how cells interpret environmental cues and offers new insight into metastatic dissemination, immune cell navigation, and the design of engineered tissues. It also provides a physical mechanism that explains contradictory observations reported in cancer invasion studies.The work highlights the importance of integrating biochemical signalling with mechanical constraints to understand how cells navigate complex environments, opening new avenues to control cell migration in health and disease.