Of Poison, Lasers, and a Little Bit of Pressure (A Science Story Outtake)

Last week, a team of physics and engineering researchers at Drexel had a new study published about the physical mechanisms underlying sickle cell disease. The study aimed to answer a question about why sickle cells don’t get stuck in the narrowest blood vessels. You can read the more detailed version (with abundant food metaphors) in the press release here, or in the scientific paper here. What ended up on the cutting room floor is a deeper explanation of how they figured that out.

First, as explained in the release, they used an artificial channel and a technique to manipulate sickle patients’ red blood cells using carbon monoxide and laser light:

Ferrone and colleagues took advantage of the fact that, for as long as they are carrying oxygen, red blood cells in sickle disease patients remain as squishy as healthy red blood cells. “They are the functional equivalent of a beanbag,” Ferrone said.

It is only after delivering their cargo to the body that hemoglobin molecules become prone to an internal reaction that turns the squishy “beanbag” cells rigid.

Here’s the part that of their method that I glossed over in the press release. It’s the part with poison and lasers.

The researchers took advantage of one other characteristic of hemoglobin molecules that made them easy to manipulate in the experiment: Hemoglobin picks up poisonous carbon monoxide gas (CO) and carries it in exactly the same way it carries oxygen. (That’s what makes CO a poison; it prevents the body from circulating oxygen by hijacking its delivery route.) In the experimental setup, researchers used CO in place of oxygen because they could force hemoglobin to drop CO it was carrying, simply by shining a bright light on it.

With this ability to force a sickle patient’s blood cell to begin turning rigid with a literal flash, the researchers set up their experiment: They parked a red blood cell from a sickle patient at the center of their artificial narrow channel while the cell was still in its flexible state. Then, by exposing the cell to a laser light, they induced the hemoglobin to drop its cargo and begin the polymerization reaction inside the cell that leads to sickling.