"It starts with the DNA, a single mutation in the gene that produces the protein hemoglobin, which carries oxygen in the blood," he explained. "The hemoglobin should be distributed homogeneously throughout the red blood cell and be able to absorb or release oxygen easily."
But with this mutation, a single amino acid in the hemoglobin protein is displaced, and as a result, the protein crystalizes and forms abnormally long chains in the cells. Similar to how water changes and forms crystals when it freezes, the protein chains change the physical and surface properties of a red blood cell, causing it to change shape and become stiff and sticky. The affected cells block blood flow.
The researchers don't know what triggers a crisis, so they are using cell stickiness as a marker of the onset. They have begun using the foundation's three-year Innovations in Clinical Research award to measure when changes in the physical properties of diseased red blood cells are associated with the painful event. For example, do sickle cells become two or three times as sticky as a normal cell when they start glomming onto one another and blocking blood vessels?
The team is also designing and building an at-home, hand-held testing device that enables patients and their doctors to monitor their blood for vital changes daily or weekly.
As designed, a patient puts a droplet of blood into the device. The blood is divided among three channels, each about half the height of a human hairthe diameter of some of the body's smallest vessels. The lining of the channels will mimic the lining of the vessels, so that interactions with the red blood cells are true to what happens inside the body.
Results come in less than 10 minutesthe time it takes for blood to flow through the channels. During that time, images and measurements of blood cells a
|Contact: Kevin Mayhood|
Case Western Reserve University