Commentary on Dynamic Cross-linking

Check out our new commentary, “Dynamic cross-links tune the solid–fluid behavior of living cells”!


To keep the mechanical integrity of an organism it seems obvious that cells, as the building blocks, must be solid. Although it is clear that switching to a fluid would be catastrophic for organization of the body, it turns out that living cells do change their mechanical properties to a more fluid-like behavior when it comes to migration and force generation. Being fluid-like allows cells to adapt to any arbitrary shape posed by the environment, which is crucial for movement through complex tissue. The mechanical integrity of healthy cells is therefore closely regulated to ensure that cells are solid enough to maintain tissue shape while also being fluid enough to allow dynamic remodeling. Physics provides powerful tools in the framework of viscoelasticity to characterize this fundamental solid and fluid-like behavior (1), and it is evident that cells need to dynamically regulate their viscoelastic properties to support physiological pressures and forces generated during lung expansion, muscle contraction, blood filtration, etc., while still allowing growth, remodeling, and repair over the lifetime of the organism. However, when this precise mechanical regulation is disturbed, cells often transition to diseased states (2). In PNAS, Ehrlicher et al. (3) study a genetic defect in the actin cross-linker alpha-actinin 4 that is known to lead to the severe kidney disease focal segmental glomerulosclerosis. Their study shows that the mutation affects cell movement, force generation, and cytoplasmic mobility, thus providing a connection between physical properties at the molecular scale and human disease.