Weak catch bonds make strong networks

Abstract

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][6][7][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][12][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][6][7][8]10,14,15 and adhesins 1,2,4,12,[16][17][18][19][20] exploit continuous redistribution to combine mechanical strength with the adaptability required for movement and proliferation 21 . Our findings provide a mechanistic understanding of 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 .Here we exploit the actin-binding protein α-actinin-4 and its K225E point mutant, associated with the heritable disease kidney focal segmental glomerulosclerosis type 1 22,25 , to identify the role of catch bonds in the mechanical properties of actin networks. Actin networks are key determinants of cell mechanics, together with other cytoskeletal proteins. To isolate the role of catch bonds in actin mechanics, we reconstitute actin networks from purified components. We first characterized the binding affinity of the two protein variants for actin .

DNA-functionalized Artificial Chimeric Mechanoreceptor for de novo Force-responsive Cellular Signalling

“…In this context, our AMR would add a band-pass force lter on biochemical recognition, enabling high molecular recognition speci city or target identi cation in speci c cell biological processes, e.g., Cl-M6PR undergoing endocytosis. The further direction is to advance the force-sensing circuit of AMR via a forcemediated DNA dynamic reaction network to rebuild the delicate natural force-discriminating strategies, e.g., catch/slip bond switch 51,52 .…”

Swelling of Homogeneous Alginate Gels with Multi-Stimuli Sensitivity

“…The bonds that strengthen under deformation are conventionally referred to as “catch” bonds [ 33 ]. The strengthening of bonds in living tissues (the phenomenon known as “the strength on demand” [ 34 ]) is explained by mechanochemical transformations (the formation and dissociation of protein–ligand complexes) in biological materials [ 35 , 36 ]. Due to the complicated nature of mechanochemical processes governing receptor–ligand interactions, attention was recently paid to the development of synthetic materials mimicking the catch bond dynamics [ 37 , 38 , 39 , 40 ].…”

Designing Superhydrophilic Hydrogels as Binder-Free Catalysts for Enhanced Oxygen Evolution Performance

“…Hydrogels are cross-linked polymers linked together by hydrophilic residues bound to water molecules in a network (such as PVA and HACC), and the hydrophobic residues are expanded by water. − This typical polymer network system endows hydrogel with the characteristics of soft texture, good dispersity, excellent stability, − and a favorable water-loving surface. , This inspired us to propose a simple method for producing superhydrophilic hydrogel catalysts for OER. To achieve this, we used poly­(vinyl alcohol) (PVA) as the backbone, a glycoprotein (glutaraldehyde, GA) as the auxiliary additive (cross-linking agent), and quaternized chitosan (HACC) as the metal anchor sites, and the transition-metal ions (Fe 3+ ) were introduced to the cross-linking process of the gel (Figure S1).…”