The researchers first used an atomic force microscope to bring the integrin molecule together with the fibronectin, then separate the two. Instruments measured the pico-newton forces required to separate the molecules, and found that the duration of the bonds increased with the repetition of the contacts.
The second technique, known as BFP, involved the use of a fibronectin-bearing glass bead attached to a red blood cell aspirated by a micropipette. Integrin expressed on the micropipette-aspirated cell was pressed into the bead, then pulled away over repeated cycles. Lifetime measurement confirmed that repeated pulling increased the longevity of the bonds.
The researchers studied two integrins, part of a family of 24 related molecules that operate in humans. In future work, they hope to determine whether or not the cyclic mechanical reinforcement they observed is a universal property of many cellular adhesion molecules.
The researchers also hope to explore how cells use this cyclic mechanical reinforcement. Because many disease processes result from abnormal cellular adhesion mechanisms, a better understanding could provide insights into how cardiovascular disease, cancer and immune system disorders operate.
"The findings of the paper have deep implications for our understanding of force-regulated signaling," added Humphries. "There is abundant biological evidence for profound effects of extracellular tensility and elasticity in controlling processes such as cancer cell proliferation and stem cell differentiation, but the mechanisms whereby this information is transduced across the outer cell membrane are unclear."
|Contact: John Toon|
Georgia Institute of Technology