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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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Mechanism of shear-resistance in simulations from Fig. 2.A) The average force per FimH and fimbriae, number of uncoiled fimbriae, and number of activated FimH at each time step (N = 15 simulations). B) The distribution of force on activated FimH bonds is shown 5 seconds after switch to each indicated shear stress. The boxes show the middle two quartiles, the whiskers the 9 to 91% range, and the plus signs the outliers (N = 14 to 98 fimbriae). Activated FimH that were under compression are indicated as zero force since we only consider tensile force here.
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pcbi-1003971-g003: Mechanism of shear-resistance in simulations from Fig. 2.A) The average force per FimH and fimbriae, number of uncoiled fimbriae, and number of activated FimH at each time step (N = 15 simulations). B) The distribution of force on activated FimH bonds is shown 5 seconds after switch to each indicated shear stress. The boxes show the middle two quartiles, the whiskers the 9 to 91% range, and the plus signs the outliers (N = 14 to 98 fimbriae). Activated FimH that were under compression are indicated as zero force since we only consider tensile force here.

Mentions: The most important observation, observed in both experiments and simulations, is that bacteria never detached, even at 25 Pa, which is higher than most physiological niches. Visual inspection of a typical simulation (e.g. Video S1) revealed the bacterium is anchored in place via one activated FimH bond at low shear, but creeps forward at increased shear, as the anchoring fimbria uncoils, until a second FimH bond is activated, and so on. We analyzed the simulations to quantify these observations. Each time the flow rate was stepped up, the mean force per bond increased suddenly (Fig. 3A), but relaxed back to about 50 pN per bond within seconds, if it had increased above this range (Fig. 3A). This drop in force corresponded to an increase in the number of uncoiled fimbriae and activated FimH bonds (Fig. 3A). Not only did the average force remain at 50 pN as shear increased further, but the distribution of bond forces was narrow (Fig. 3B). It was shown previously that FimH bonds are long-lived between 30 and 70 pN, but break within seconds above 90 pN [41] because of the exponential effects of force, so we consider bonds exposed to over 90 pN force as vulnerable to dissociation. There were almost no vulnerable bonds in these simulations, as indicated by the presence of only one symbol above the dotted line at 90 pN in Fig. 3A. Thus, bacteria in the simulations withstand high shear stress by recruiting more activated bonds and by distributing the force evenly across these bonds.


Yielding elastic tethers stabilize robust cell adhesion.

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

Mechanism of shear-resistance in simulations from Fig. 2.A) The average force per FimH and fimbriae, number of uncoiled fimbriae, and number of activated FimH at each time step (N = 15 simulations). B) The distribution of force on activated FimH bonds is shown 5 seconds after switch to each indicated shear stress. The boxes show the middle two quartiles, the whiskers the 9 to 91% range, and the plus signs the outliers (N = 14 to 98 fimbriae). Activated FimH that were under compression are indicated as zero force since we only consider tensile force here.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1003971-g003: Mechanism of shear-resistance in simulations from Fig. 2.A) The average force per FimH and fimbriae, number of uncoiled fimbriae, and number of activated FimH at each time step (N = 15 simulations). B) The distribution of force on activated FimH bonds is shown 5 seconds after switch to each indicated shear stress. The boxes show the middle two quartiles, the whiskers the 9 to 91% range, and the plus signs the outliers (N = 14 to 98 fimbriae). Activated FimH that were under compression are indicated as zero force since we only consider tensile force here.
Mentions: The most important observation, observed in both experiments and simulations, is that bacteria never detached, even at 25 Pa, which is higher than most physiological niches. Visual inspection of a typical simulation (e.g. Video S1) revealed the bacterium is anchored in place via one activated FimH bond at low shear, but creeps forward at increased shear, as the anchoring fimbria uncoils, until a second FimH bond is activated, and so on. We analyzed the simulations to quantify these observations. Each time the flow rate was stepped up, the mean force per bond increased suddenly (Fig. 3A), but relaxed back to about 50 pN per bond within seconds, if it had increased above this range (Fig. 3A). This drop in force corresponded to an increase in the number of uncoiled fimbriae and activated FimH bonds (Fig. 3A). Not only did the average force remain at 50 pN as shear increased further, but the distribution of bond forces was narrow (Fig. 3B). It was shown previously that FimH bonds are long-lived between 30 and 70 pN, but break within seconds above 90 pN [41] because of the exponential effects of force, so we consider bonds exposed to over 90 pN force as vulnerable to dissociation. There were almost no vulnerable bonds in these simulations, as indicated by the presence of only one symbol above the dotted line at 90 pN in Fig. 3A. Thus, bacteria in the simulations withstand high shear stress by recruiting more activated bonds and by distributing the force evenly across these bonds.

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