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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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Ability of bacteria to withstand variable flow conditions.A) Cartoon of simulated bacteria suspended between multiple fimbriae after shear stress is decreased from 25 to 0.01 Pa (from left to right). Bonds that are activated and not activated are shown as red and green balls, respectively, and uncoiled sections of fimbriae as thin white lines. B) Number of uncoiled fimbriae and activated bonds at the indicated shear stress before and after a decrease to 0.01 Pa in simulations. (Error bars  =  SD, N = 33 to 44 bacteria). C) Fraction of bacteria remaining bound over time after a decrease from the indicated shear stress to 0.01 Pa in simulations (N = 33 to 44) and experiments (N = 36 to 90).
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pcbi-1003971-g005: Ability of bacteria to withstand variable flow conditions.A) Cartoon of simulated bacteria suspended between multiple fimbriae after shear stress is decreased from 25 to 0.01 Pa (from left to right). Bonds that are activated and not activated are shown as red and green balls, respectively, and uncoiled sections of fimbriae as thin white lines. B) Number of uncoiled fimbriae and activated bonds at the indicated shear stress before and after a decrease to 0.01 Pa in simulations. (Error bars  =  SD, N = 33 to 44 bacteria). C) Fraction of bacteria remaining bound over time after a decrease from the indicated shear stress to 0.01 Pa in simulations (N = 33 to 44) and experiments (N = 36 to 90).

Mentions: Bacteria in vivo are often exposed to variable shear stress due to intestinal peristalsis or salivary motion. Bacteria binding via FimH catch bonds were shown previously to detach when the flow is turned down from 2 to 0.01 Pa [42], presumably because catch bonds detach at low force. However, in our current study, bacteria relaxed backwards but did not detach when shear stress was dropped from 25 to 0.01 Pa, in both experiments or in simulations (Fig. 2). Surprisingly, the number of activated bonds increased when shear stress dropped to 0.01 Pa (Fig. 3A). Moreover, while the drag force on a bacterium at 0.01 Pa is only 0.2 pN, the force per bond did not drop to near zero, but rather remained tightly distributed around 30 pN (Fig. 3B). Simulations show that the uncoiled fimbriae shorten when shear is decreased, pulling the bacterium backwards, and activating new bonds as the bacterium becomes suspended between partially uncoiled fimbriae pulling in opposite directions (Fig. 5A and Video S1). Since the bacterium is now stationary, the anchoring bond is subjected to the equilibrium uncoiling force (32.2 pN) for all partially uncoiled fimbriae.


Yielding elastic tethers stabilize robust cell adhesion.

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

Ability of bacteria to withstand variable flow conditions.A) Cartoon of simulated bacteria suspended between multiple fimbriae after shear stress is decreased from 25 to 0.01 Pa (from left to right). Bonds that are activated and not activated are shown as red and green balls, respectively, and uncoiled sections of fimbriae as thin white lines. B) Number of uncoiled fimbriae and activated bonds at the indicated shear stress before and after a decrease to 0.01 Pa in simulations. (Error bars  =  SD, N = 33 to 44 bacteria). C) Fraction of bacteria remaining bound over time after a decrease from the indicated shear stress to 0.01 Pa in simulations (N = 33 to 44) and experiments (N = 36 to 90).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003971-g005: Ability of bacteria to withstand variable flow conditions.A) Cartoon of simulated bacteria suspended between multiple fimbriae after shear stress is decreased from 25 to 0.01 Pa (from left to right). Bonds that are activated and not activated are shown as red and green balls, respectively, and uncoiled sections of fimbriae as thin white lines. B) Number of uncoiled fimbriae and activated bonds at the indicated shear stress before and after a decrease to 0.01 Pa in simulations. (Error bars  =  SD, N = 33 to 44 bacteria). C) Fraction of bacteria remaining bound over time after a decrease from the indicated shear stress to 0.01 Pa in simulations (N = 33 to 44) and experiments (N = 36 to 90).
Mentions: Bacteria in vivo are often exposed to variable shear stress due to intestinal peristalsis or salivary motion. Bacteria binding via FimH catch bonds were shown previously to detach when the flow is turned down from 2 to 0.01 Pa [42], presumably because catch bonds detach at low force. However, in our current study, bacteria relaxed backwards but did not detach when shear stress was dropped from 25 to 0.01 Pa, in both experiments or in simulations (Fig. 2). Surprisingly, the number of activated bonds increased when shear stress dropped to 0.01 Pa (Fig. 3A). Moreover, while the drag force on a bacterium at 0.01 Pa is only 0.2 pN, the force per bond did not drop to near zero, but rather remained tightly distributed around 30 pN (Fig. 3B). Simulations show that the uncoiled fimbriae shorten when shear is decreased, pulling the bacterium backwards, and activating new bonds as the bacterium becomes suspended between partially uncoiled fimbriae pulling in opposite directions (Fig. 5A and Video S1). Since the bacterium is now stationary, the anchoring bond is subjected to the equilibrium uncoiling force (32.2 pN) for all partially uncoiled fimbriae.

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