Researchers Provide First Experimental Evidence of "Catch Bonds" Key to Controlling Cell Adhesion

Known as "catch bonds," the adhesion mechanism displays surprising behavior, prolonging rather than shortening the lifetimes of bonds between specific molecules as increasing force is applied. Proposed theoretically nearly 15 years ago, catch bonds could help explain how the body regulates the activity of white blood cells, which must flow freely through blood vessels -- yet bond to injury sites despite blood flow forces.

Understanding how catch bonds work could offer drug designers a new target for anti-inflammatory and anti-thrombosis compounds, and potentially provide a new approach to controlling the metastasis process that cancers use to spread.

"Before the experimental demonstration of catch bonds, we tended to think that force could regulate biochemical reactions only in one direction," said Cheng Zhu, a professor in the School of Mechanical Engineering at the Georgia Institute of Technology. "This work demonstrates that force can alter the rate in the other direction, depending on the type of interaction. In this post-genome era, we need to know more about how proteins interact with one another and with DNA. This work illustrates a new regulatory mechanism for how proteins - which from a mechanical engineer's perspective are nanomachines - operate."

Supported by the National Institutes of Health (NIH), the research involves two teams of scientists, one at Georgia Tech and Emory University in Atlanta, and the other at the Oklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center in Oklahoma City. A paper describing the work was published in the May 8 issue of the journal Nature.

The researchers studied the activity of selectin molecules, a family of proteins that helps control the adhesion of white blood cells - leukocytes - used by the body to fight infection and repair injuries. Before they can respond to injury or infection, leukocytes must first tether to and then roll along the wall of a blood vessel. While tethered, the cells receive signals instructing them to enter underlying tissue to fight pathogens or repair injuries. The selectins control the first stage of that process, causing the leukocytes to drop out of the bloodstream and begin attaching to blood vessel walls.

In two separate but complementary experiments, the researchers found evidence of catch bonds operating within the complex of P-selectin and its ligand PSGL-1.