| A bacterial appendage has evolved to bind to epithelial cells much more strongly with increasing mechanical force. |
This intentional tightening and loosening of your grip is easy enough to carry out, and you do it without thinking. It turns out that, broadly speaking, many cells must do essentially the same thing, but with protein appendages rather than hands (and, obviously, in the absence of thought, because individual cells don't "think").
When most scientists envision a bacterial cell sticking to a surface, such as within an internal organ, they probably think of a slowly-moving cell gently latching onto its target. This is often an inaccurate vision, given that the surrounding fluid (e.g. blood) may be moving quickly, or the surface itself may be moving (e.g. as in bladder stretching).
At first glance, this fluid motion would seem to necessitate strong chemical binding to withstand forces that would otherwise break the bond (disrupt cell attachment). This is in contrast to the need for weak attachment, to enable the bacterium to move along the surface.
A catch bond mechanism resolves these conflicting needs, a noncovalent bonding mechanism in which the chemical bond becomes stronger under force (reminiscent of a Chinese finger trap, although clearly not the exact same thing). Evgeni Sokurenko (University of Washington, United States) and coworkers have explored this feature of Escherichia coli cells by investigating how a cellular appendage (linkages of "Fim" proteins) is adapted to switch binding strengths to epithelial cells (cell line T24) in response to fluid flow.
Confirming appendage function.
The scientists first found that more bacterial cells bind to urinary epithelial cells when the shear stress is 0.1, rather than 0.01, Pascals (this is probably within the physiological range seen in the human bladder). Over twenty times as many bacterial cells are bound to the epithelial cells at the higher shear stress.
A broadly similar effect is seen when the bacterial appendages are extracted from the cells and affixed to beads, and the experiment is repeated with an artificial surface coated with mannose (the sugar to which the appendages bind). Not surprisingly, the effect is smaller due to the artificial construction, but this strongly suggests the mechanism of enhanced binding.
How strongly do the bacterial cells resist detachment when the shear stress increases? Using atomic force microscopy (pulling a small tip away from the cellular appendage), the scientists found that the bacteria were less likely to break away when the force was increased from 30 to 80 picoNewtons, e.g. 45% of them pulling away at 30 picoNewtons relative to less than 10% from 40 to 80 picoNewtons force.
Such behavior is commonly accepted to be a defining feature of catch bonds. The scientists then used molecular dynamics simulations to uncover the structural features of the bacterial appendages that enable such behavior (direct experimental approaches, e.g. nuclear magnetic resonance spectroscopy, are challenging).
Simulation highlights.
The scientists found that the protein appendage can be in either an elongated or a twisted conformation. The elongated form strongly binds to mannose, and the twisted form binds to mannose less strongly.
These conformational states are related how the binding domain is linked to the rest of the protein appendage. Therefore, strength of binding is related to binding domain attachment to the rest of the protein appendage.
More specifically, at lower forces, the binding domain is a hook-shaped structure. Other flexible components of the appendage permit surface exploration (i.e. weak binding).
At higher forces, the entire protein appendage is extended, with retained rotational freedom. This probably reduces the twisting forces induced by binding to the surface, and stabilizes the bond (i.e. strengthening binding under flow).
Figure 7 in the original manuscript (open access) illustrates this concept in a cartoon diagram. Quantitative results (e.g. twist angle with an applied force) and a far more detailed discussion are provided in the original manuscript for those of you who are interested (my brief blurb of a summary doesn't even begin to do the manuscript justice).
Future directions.
How common is catch bonding in the cellular world? The scientists point out that it's probably an uncommon mechanism for relatively permanent binding, e.g. as in biofilms.
However, the scientists also point out that many bacterial and other cells feature catch bonding, and many of the relevant adhesion proteins possess the general features of a hook shape and multiple subunits described here. Many other protein complexes of similar nature, e.g. cell matrix proteins, may be optimized for strengthened adhesion during fluid flow or cellular contraction, a question for future research.
NOTE: The scientists' research was funded directly by the National Institutes of Health, and indirectly by the American Heart Association.
Aprikian, P., Interlandi, G., Kidd, B. A., Le Trong, I., Tchesnokova, V., Yakovenko, O., Whitfield, M. J., Bullitt, E., Stenkamp, R. E., Thomas, W. E., & Sokurenko, E. V. (2011). The Bacterial Fimbrial Tip Acts as a Mechanical Force Sensor PLoS Biology, 9 (5) DOI: 10.1371/journal.pbio.1000617