"It's known that if EGFR is over-active, that can lead to cancer," Salaita says. "And one of the ways that EGFR is activated is by binding its ligand and taking it in. So if we can understand how tugging on EGFR force changes the pathway, and whether it plays a role in cancer, it might be possible to design drugs that target this pulling process."
Several methods have been developed in recent years to try to study the mechanics of cellular forces, but they have major limitations.
One genetic engineering approach requires splitting open and modifying proteins of a cell. This invasive technique may change the behavior of the cell, skewing the results.
The technique developed at Emory is non-invasive, does not modify the cell, and can be done with a standard florescence microscope. A flexible polymer is chemically modified at both ends. One end gets a florescence-based turn-on sensor that will bind to a receptor on the cell surface. The other end is chemically anchored to a microscope slide and a molecule that quenches fluorescence.
"Once a force is applied to the polymer, it stretches out," Salaita explains. "And as it extends, the distance from the quencher increases and the fluorescent signal turns on and grows brighter. We can determine the force being exerted by measuring the amount of fluorescent light emitted."
The forces of any individual protein or molecule on the cell surface can be measured using the technique, at far higher spatial and temporal resolutions than was previously possible.
Many mysteries beyond the biology and chemistry of cells may be explained through measuring cellular forces. How does a cancer cell crawl when a tumor spreads? What are the forces involved in cell division and immune response? What are the mechanics that allow groups of cardiac cells to beat in unison?
|Contact: Beverly Clark|