Weak catch bonds make strong networks

Abstract

Molecular catch bonds are ubiquitous in biology and well-studied in the context of leukocyte extravasion1, cellular mechanosensing2,3, and urinary tract infection4. 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 flows1,4, and hence provides ‘strength-on-demand’. Recently, cytoskeletal crosslinkers have been discovered that also display catch bonding5–8. It has been suggested that they strengthen cells, following the strength-on-demand paradigm9,10. However, catch bonds tend to be weaker compared to regular (slip) bonds because they have cryptic binding sites that are often inactive11–13. 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 cytolinkers5–8,10,14,15 and adhesins1,2,4,12,16–20 exploit continuous redistribution to combine mechanical strength with the adaptability required for movement and proliferation21. Our findings provide a mechanistic understanding of diseases where catch bonding is compromised11,12 such as kidney focal segmental glomerulosclerosis22,23, caused by the α-actinin-4 mutant studied here. Moreover, catch bonds provide a route towards creating life-like materials that combine strength with deformability24.

An actin mechanostat ensures hyphal tip sharpness in Phytophthora infestans to achieve host penetration

“…In reconstituted actin networks, studied in vitro, it was found that the mechano-sensitive ARP2/3 complex, which creates branch points in actin filaments, results in force-induced network densification and stiffening ( 61 ). Also, catch bonding cross-linkers, such as α-actinin, whose bonding strength with actin filaments grows under the action of mechanical stress, can result in force-gated accumulation and filament bundling ( 64 , 65 ). Cross-linking actin with these proteins does not result in aster formation, which implies that a more complex mechanism involving multiple regulators is at play in the mechanostat.…”

On the role of mechanosensitive binding dynamics in the pattern formation of active surfaces

“…Numerous experimental findings have highlighted the key role of actin cross-linkers as key regulators of actin cortex mechanics in cells. In addition, experimental evidence is increasing that actin cross-linker binding dynamics is by itself mechanosensitive [20][21][22][23][24] . Here, we investigated the influence of mechanosensitive molecular regulators on pattern formation and deformation of active spherical surfaces.…”

“…Motivated by experimental observations, see e.g. [21][22][23][24] , we anticipate that the unbinding rate of molecular regulators of active stress depends on the local trace of the in-plane stress t i i . In particular, we make the choice of a Bell model dependence…”

“…Furthermore, the degree of cross-linking of actin networks was shown to sensitively tune the network's mechanical resistance towards shear deformations 18,19 . In recent years, several experimental studies have provided direct or indirect evidence that actin cross-linkers exhibit mechanosensitive binding dynamics [20][21][22][23][24][25] . In particular, two scenarios have been suggested for cross-linker binding to actin 23,24 ; i) tension-induced increase of bond lifetimes -also called catch bond behavior and ii) tension-induced decrease of bond lifetimes -also called slip bond behavior.…”

“…In recent years, several experimental studies have provided direct or indirect evidence that actin cross-linkers exhibit mechanosensitive binding dynamics [20][21][22][23][24][25] . In particular, two scenarios have been suggested for cross-linker binding to actin 23,24 ; i) tension-induced increase of bond lifetimes -also called catch bond behavior and ii) tension-induced decrease of bond lifetimes -also called slip bond behavior. Therefore, in a cortex model that captures mechanosensitivity of stress-regulating cortical molecules, the unbinding rate of such molecules needs to depend on the local mechanical stress in the cortical surface.…”