Weak catch bonds make strong networks

Molecular catch bonds are ubiquitous in biology and well-studied in the context of leukocyte extravasion 1 , cellular mechanosensing 2,3 , and urinary tract infection 4 . Unlike normal (slip) bonds, catch bonds strengthen under tension. The current paradigm is that this remarkable ability enables cells to increase their adhesion in fast fluid flows 1,4 , and hence provides ‘strength-on-demand’. Recently, cytoskeletal crosslinkers have been discovered that also display catch bonding 5–8 . It has been suggested that they strengthen cells, following the strength-on-demand paradigm 9,10 . However, catch bonds tend to be weaker compared to regular (slip) bonds because they have cryptic binding sites that are often inactive 11–13 . Therefore, the role of catch bonding in the cytoskeleton remains unclear. Here we reconstitute cytoskeletal actin networks to show that catch bonds render them both stronger and more deformable than slip bonds, even though the bonds themselves are weaker. We develop a model to show that weak binding allows the catch bonds to mitigate crack initiation by moving from low- to high-tension areas in response to mechanical loading. By contrast, slip bonds remain trapped in stress-free areas. We therefore propose that the mechanism of catch bonding is typified by dissociation-on-demand rather than strength-on-demand. Dissociation-on-demand can explain how both cytolinkers 5–8,10,14,15 and adhesins 1,2,4,12,16–20 exploit continuous redistribution to combine mechanical strength with the adaptability required for movement and proliferation 21 . Our findings provide a new perspective on diseases where catch bonding is compromised 11,12 such as kidney focal segmental glomerulosclerosis 22,23 , caused by the α-actinin-4 mutant studied here. Moreover, catch bonds provide a route towards creating life-like materials that combine strength with deformability 24 .