Cells constantly need to adapt to extracellular clues that require changes in their actin-based structures, but it is unclear how these are integrated into a cellular network. In this work, Laurent Blanchoin, Manuel Théry and co-workers (Senger et al., 2019) investigate the mechanical interplay between the actin network architecture of a cell and the geometry of its environment by controlling cell shape with the use of adhesive micropatterns. They show here that the actin crosslinker α-actinin is required for the stereotypical symmetric actin architecture of cells plated on a crossbow pattern, as knockdown of both the α-actinin isoforms α-actinin-1 and α-actinin-4, results in a disorganised actin network with compromised symmetry, as well as perturbed retrograde actin flow. Furthermore, myosin II also exhibits an asymmetric distribution upon α-actinin depletion, with concomitant defects in force transmission across the cell, as determined by traction force microscopy. Finally, the authors use in situ micropatterning to measure cell responses to adhesive cues in real time. Interestingly, control cells are able to compare regions with dense and sparse adhesion sites and choose to form protrusions towards the denser regions, whereas α-actinin-depleted cells are unable to integrate this information and only protrude randomly. On the basis of these findings, the authors propose that α-actinin is crucial for the spatial integration of mechanical forces that establishes intracellular actin network symmetry in response to extracellular cues.
