Catch bond

Catch bonds were suspected for many years to play a role in the rolling of leukocytes, being strong enough to roll in presence of high forces caused by high shear stresses, while avoiding getting stuck in capillaries where the fluid flow, and therefore shear stress, is low.

[4] Catch bonds were first proposed in 1988 in the Proceedings of the Royal Society by M. Dembo et al. while at Los Alamos National Laboratory.

[5] Slip bonds represent the ordinary behavior originally modeled by G. Bell, Dembo's former postdoctoral mentor at Los Alamos National Laboratory in 1978.

[6] These finding prompted the discoveries of other important catch bonds in the 2000s, including those between L-selectin and PSGL-1 or endoglycan,[7] FimH and mannose,[2] myosin and actin,[8] platelet glycoprotein Ib and von Willebrand factor,[9] and integrin alpha 5 beta 1 and fibronectin.

[10] Emphasizing their importance and general acceptance, in the three years following their discovery there were at least 24 articles published on catch bonds.

[22] Sivasankar and his research team have found that the mechanism behind the puzzling phenomenon is due to long-lived, force-induced hydrogen bonds.

Using data from previous experiments, the team used molecular dynamics to discover that two rod-shaped cadherins in an X-dimer formed catch bonds when pulled and in the presence of calcium ions.

[23] The calcium ions keep the cadherins rigid, while pulling brings the proteins closer together, allowing for hydrogen bonds to form.

According to the researchers, "Robust cadherin adhesion is essential for maintaining the integrity of tissue such as the skin, blood vessels, cartilage and muscle that are exposed to continuous mechanical assault."

An interesting recent development is the discoveries of catch bonds formed between signaling receptors and their ligands.

This has indeed been observed for interactions of P-selectin with PSGL-1 or anti-P-selectin antibody,[42] L-selectin with PSGL-1,[43] myosin with actin,[8] integrin alpha V beta 3 with fibrinogen,[44] and TCR with pMHC.

During this process, leukocytes move through the circulatory system to sites of infection, and in doing so they 'roll' and bind to selectin molecules on the vessel wall.

[46] Multiple sources of evidence have shown that catch bonds are responsible for the tether and roll mechanism that allows this critical process to occur.

At low shear stress above the threshold of about .3 to 5 dynes per squared centimeter, leukocytes alternate between binding and non-binding.

As the shear stress continue to increase, the selectin bonds becomes stronger, causing the rolling velocity to be slower.

Researchers have hypothesized that the ability of leukocytes to maintain attachment and rolling on the blood vessel wall can be explained by a combination of many factors, including cell flattening to maintain a larger binding surface-area and reduce hydrodynamic drag, as well as tethers holding the rear of the rolling cell to the endothelium breaking and slinging to the front of the rolling cell to reattach to the endothelial wall.

[4] Therefore, the weak binding of a sling at the leading edge of a rolling leukocyte would initially be strengthened as the cell rolls farther and the tension on the bond increases, preventing the cell from dissociating from the endothelial wall and floating freely in the bloodstream despite high shear forces.

[51] As a result of this conformational change, the ligand is effectively locked in place despite tension exerted on the bond.

As the force exerted starts to increase, the dissociation constant decreases, causing binding to become stronger.

[4] Catch bonds also play a significant role in bacterial adhesion, most notably in Escherichia coli.

This shear stress threshold is about 1 dynes per squared centimeter, slightly larger than that of selectin binding.