Frustrated binding of biopolymer crosslinkers

Mulla, Yuval; Wierenga, Harmen; Alkemade, Celine; Wolde, Pieter Rein ten; Koenderink, Gijsje H.

doi:10.1039/c8sm02429d

Cited by 9 publications

(14 citation statements)

References 45 publications

(54 reference statements)

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“…We compare catch bonds with slip bonds, which do not require force-activation for strong binding , keeping all other parameters identical (see Extended Data Table 1 for the full list of parameters used for each simulation). To account for the mobility by random diffusion of the linkers after unbinding, we allow for unbound linkers to rebind at a random new location 32,34 . As the actin concentration is much larger than the crosslinker concentration both in our reconstituted networks (48 μM versus 0.48 μM, respectively) and in living cells (∼100 μM versus ∼1 μM, respectively 54 ), we consider 10-fold more binding sites than crosslinkers to prevent competition for actin-binding sites.…”

Section: Methodsmentioning

confidence: 99%

“…Actin was purified from rabbit psoas skeletal muscle as described in reference 34 , including the gel filtration step to remove oligomers. The concentration was determined by measuring the optical absorbance at 280 nm.…”

Section: Methodsmentioning

confidence: 99%

“…The laser intensity during imaging was chosen such that the reference intensity dropped less than 5% during the recovery phase. To extract a timescale for fluorescence recovery, τ FRAP , the time-dependent intensity normalized by the intensity of the reference area was fitted with a single exponential function: , where I 0 is the intensity directly after bleaching 34 .…”

Section: Methodsmentioning

confidence: 99%

“…Weak catch bonds make strong networks Yuval Mulla 1,2 , Mario J Avellaneda , Antoine Roland 1 , Lucia Baldauf 1,3 , Sander J Tans 1,3 *, Gijsje H Koenderink 1,3 *…”

Section: Extended Data Figuresmentioning

confidence: 99%

“…We tune the relaxation frequency for actin networks crosslinked with K255E by increasing the temperature 3 from 10 º C to 25 º C such that it equals the peak frequency of networks crosslinked with the wild type variant at low temperature (10 º C). Now, the time-dependent linear rheology of both networks is indistinguishable even without normalizing the frequency (Extended Data Fig.…”

Section: Supplementary Informationmentioning

confidence: 99%

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Weak catch bonds make strong networks

Mulla

Avellaneda²,

Roland³

et al. 2020

Preprint

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Weak catch bonds make strong networks Yuval Mulla 1,2 , Mario J Avellaneda , Antoine Roland 1 , Lucia Baldauf 1,3 , Sander J Tans 1,3 *, Gijsje H Koenderink 1,3 *…”

Section: Extended Data Figuresmentioning

confidence: 99%

Section: Supplementary Informationmentioning

confidence: 99%

See 3 more Smart Citations

Weak catch bonds make strong networks

Mulla

Avellaneda²,

Roland³

et al. 2020

Preprint

Self Cite

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Binding Dynamics of α-Actinin-4 in Dependence of Actin Cortex Tension

Hosseini

Sbosny

Poser

et al. 2020

Biophysical Journal

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Mechano-sensation of cells is an important prerequisite for cellular function, e.g. in the context of cell migration, tissue organisation and morphogenesis. An important mechano-chemical-transducer is the actin cytoskeleton. In fact, previous studies have shown that actin cross-linkers, such as α-actinin-4, exhibit mechanosensitive properties in its binding dynamics to actin polymers. However, to date, a quantitative analysis of tension-dependent binding dynamics in live cells is lacking. Here, we present a new technique that allows to quantitatively characterize the dependence of cross-linking lifetime of actin cross-linkers on mechanical tension in the actin cortex of live cells. We use an approach that combines parallel plate confinement of round cells, fluorescence recovery after photo-bleaching, and a mathematical mean-field model of cross-linker binding. We apply our approach to the actin cross-linker α-actinin-4 and show that the cross-linking time of α-actinin-4 homodimers increases approximately twofold within the cellular range of cortical mechanical tension rendering α-actinin-4 a catch bond in physiological tension ranges.

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Weak catch bonds make strong networks

et al. 2022

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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 .

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Frustrated binding of biopolymer crosslinkers

Cited by 9 publications

References 45 publications

Weak catch bonds make strong networks

Weak catch bonds make strong networks

Binding Dynamics of α-Actinin-4 in Dependence of Actin Cortex Tension

Weak catch bonds make strong networks

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