When cells sense a mechanical force, they respond by regulating signalling pathways that affect migration, polarisation and other functions – a process known as mechanotransduction. Many questions remain about how force is transduced, and Christoph Ballestrem, Ralf Kemkemer and colleagues () now identify key mechanistic differences between force-induced cell polarisation and migration. The authors first show that, in response to stretching forces, NIH3T3 cells realign actin filaments, focal adhesions (FAs) and microtubules (MTs) perpendicularly to the direction of stretch; notably, cellular reorientation requires an intact actin cytoskeleton but does not depend on MT function. By contrast, stretch-induced cell migration does require dynamic MTs. The authors next show that the activity of the GTPase RhoA (which regulates the actin cytoskeleton) increases dramatically in response to stretch; again, this effect is independent of intact MTs. Finally, FA reorganisation during force-induced polarisation occurs through an MT-independent sliding mechanism; by contrast, MTs are known to regulate FA dynamics during cell migration. The authors conclude that – despite the important role of MTs in cell migration – force-induced polarisation is largely MT-independent. Their results highlight the complexity of cellular signalling in response to force.
