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Yielding elastic tethers stabilize robust cell adhesion.

Whitfield MJ, Luo JP, Thomas WE - PLoS Comput. Biol. (2014)

Bottom Line: In contrast, strain-hardening and linear elastic tethers concentrate force on the most vulnerable bonds, which leads to failure of the entire adhesive contact.Load distribution is especially important to noncovalent receptor-ligand bonds, because they become exponentially shorter lived at higher force above a critical force, even if they form catch bonds.The advantage of yielding is likely to extend to any blood cells or pathogens adhering in flow, or to any situation where bonds are stretched unequally due to surface roughness, unequal native bond lengths, or conditions that act to unzip the bonds.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, University of Washington, Seattle, Washington, United States of America.

ABSTRACT
Many bacteria and eukaryotic cells express adhesive proteins at the end of tethers that elongate reversibly at constant or near constant force, which we refer to as yielding elasticity. Here we address the function of yielding elastic adhesive tethers with Escherichia coli bacteria as a model for cell adhesion, using a combination of experiments and simulations. The adhesive bond kinetics and tether elasticity was modeled in the simulations with realistic biophysical models that were fit to new and previously published single molecule force spectroscopy data. The simulations were validated by comparison to experiments measuring the adhesive behavior of E. coli in flowing fluid. Analysis of the simulations demonstrated that yielding elasticity is required for the bacteria to remain bound in high and variable flow conditions, because it allows the force to be distributed evenly between multiple bonds. In contrast, strain-hardening and linear elastic tethers concentrate force on the most vulnerable bonds, which leads to failure of the entire adhesive contact. Load distribution is especially important to noncovalent receptor-ligand bonds, because they become exponentially shorter lived at higher force above a critical force, even if they form catch bonds. The advantage of yielding is likely to extend to any blood cells or pathogens adhering in flow, or to any situation where bonds are stretched unequally due to surface roughness, unequal native bond lengths, or conditions that act to unzip the bonds.

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Effect of different fimbrial elastic properties in simulations in which shear stress is increased linearly.A) Percent of simulated bacteria that remain bound (N = 19). B) Average number of activated FimH bonds on remaining bacteria. C) Force per activated FimH. (Error bars  =  SD, N = 12 to 61 fimbriae). D) Distribution of force on activated FimH bonds for same fimbriae as panel C. Box and whisker representation is the same as in Fig. 3. In all panels, black  =  yielding, cyan  =  linear, and orange  =  strain hardening elasticity.
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pcbi-1003971-g004: Effect of different fimbrial elastic properties in simulations in which shear stress is increased linearly.A) Percent of simulated bacteria that remain bound (N = 19). B) Average number of activated FimH bonds on remaining bacteria. C) Force per activated FimH. (Error bars  =  SD, N = 12 to 61 fimbriae). D) Distribution of force on activated FimH bonds for same fimbriae as panel C. Box and whisker representation is the same as in Fig. 3. In all panels, black  =  yielding, cyan  =  linear, and orange  =  strain hardening elasticity.

Mentions: We next asked whether the nonlinear elasticity of the fimbriae was necessary for bacteria to resist high shear stresses. In the simulations, we changed the elastic properties of the fimbriae to model native yielding elasticity, strain-hardening elasticity, or linear elasticity. Shear stress was increased at 1 Pa/s until 100 Pa, or until the bacteria detached. If only one fimbria was allowed to attach (by setting the bond association rate to zero for the unbound fimbriae), then bacteria detached between 10 and 12 Pa for all regardless of the type of tether (Fig. 4A, dashed lines). Allowing multiple fimbriae to bind provided a small improvement for bacteria with strain-hardening tethers, which all detached between 10 and 18 Pa (Video S2), and slightly more improvement to bacteria with linear elastic tethers (Video S3), which detached between 15 and 25 Pa (Fig. 4A). In contrast, bacteria with multiple native yielding tethers withstood much higher shear stress, with very few detaching by 30 Pa, and over 50% remaining bound through 100 Pa (Video S4). Thus, multiple tethers with yielding elasticity were necessary in the simulations to reproduce the ability of bacteria to withstand over 25 Pa, which was observed experimentally.


Yielding elastic tethers stabilize robust cell adhesion.

Whitfield MJ, Luo JP, Thomas WE - PLoS Comput. Biol. (2014)

Effect of different fimbrial elastic properties in simulations in which shear stress is increased linearly.A) Percent of simulated bacteria that remain bound (N = 19). B) Average number of activated FimH bonds on remaining bacteria. C) Force per activated FimH. (Error bars  =  SD, N = 12 to 61 fimbriae). D) Distribution of force on activated FimH bonds for same fimbriae as panel C. Box and whisker representation is the same as in Fig. 3. In all panels, black  =  yielding, cyan  =  linear, and orange  =  strain hardening elasticity.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4256016&req=5

pcbi-1003971-g004: Effect of different fimbrial elastic properties in simulations in which shear stress is increased linearly.A) Percent of simulated bacteria that remain bound (N = 19). B) Average number of activated FimH bonds on remaining bacteria. C) Force per activated FimH. (Error bars  =  SD, N = 12 to 61 fimbriae). D) Distribution of force on activated FimH bonds for same fimbriae as panel C. Box and whisker representation is the same as in Fig. 3. In all panels, black  =  yielding, cyan  =  linear, and orange  =  strain hardening elasticity.
Mentions: We next asked whether the nonlinear elasticity of the fimbriae was necessary for bacteria to resist high shear stresses. In the simulations, we changed the elastic properties of the fimbriae to model native yielding elasticity, strain-hardening elasticity, or linear elasticity. Shear stress was increased at 1 Pa/s until 100 Pa, or until the bacteria detached. If only one fimbria was allowed to attach (by setting the bond association rate to zero for the unbound fimbriae), then bacteria detached between 10 and 12 Pa for all regardless of the type of tether (Fig. 4A, dashed lines). Allowing multiple fimbriae to bind provided a small improvement for bacteria with strain-hardening tethers, which all detached between 10 and 18 Pa (Video S2), and slightly more improvement to bacteria with linear elastic tethers (Video S3), which detached between 15 and 25 Pa (Fig. 4A). In contrast, bacteria with multiple native yielding tethers withstood much higher shear stress, with very few detaching by 30 Pa, and over 50% remaining bound through 100 Pa (Video S4). Thus, multiple tethers with yielding elasticity were necessary in the simulations to reproduce the ability of bacteria to withstand over 25 Pa, which was observed experimentally.

Bottom Line: In contrast, strain-hardening and linear elastic tethers concentrate force on the most vulnerable bonds, which leads to failure of the entire adhesive contact.Load distribution is especially important to noncovalent receptor-ligand bonds, because they become exponentially shorter lived at higher force above a critical force, even if they form catch bonds.The advantage of yielding is likely to extend to any blood cells or pathogens adhering in flow, or to any situation where bonds are stretched unequally due to surface roughness, unequal native bond lengths, or conditions that act to unzip the bonds.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioengineering, University of Washington, Seattle, Washington, United States of America.

ABSTRACT
Many bacteria and eukaryotic cells express adhesive proteins at the end of tethers that elongate reversibly at constant or near constant force, which we refer to as yielding elasticity. Here we address the function of yielding elastic adhesive tethers with Escherichia coli bacteria as a model for cell adhesion, using a combination of experiments and simulations. The adhesive bond kinetics and tether elasticity was modeled in the simulations with realistic biophysical models that were fit to new and previously published single molecule force spectroscopy data. The simulations were validated by comparison to experiments measuring the adhesive behavior of E. coli in flowing fluid. Analysis of the simulations demonstrated that yielding elasticity is required for the bacteria to remain bound in high and variable flow conditions, because it allows the force to be distributed evenly between multiple bonds. In contrast, strain-hardening and linear elastic tethers concentrate force on the most vulnerable bonds, which leads to failure of the entire adhesive contact. Load distribution is especially important to noncovalent receptor-ligand bonds, because they become exponentially shorter lived at higher force above a critical force, even if they form catch bonds. The advantage of yielding is likely to extend to any blood cells or pathogens adhering in flow, or to any situation where bonds are stretched unequally due to surface roughness, unequal native bond lengths, or conditions that act to unzip the bonds.

Show MeSH
Related in: MedlinePlus