Because their job is so simple, red blood cells don’t need much metabolism. That means they carry few of the necessary proteins for generating energy. Nor do they need to burn fuel and pump out waste. A true cell pumps its fuel in and spits its trash out by means of elaborate channels and bubbles that can shuttle molecules across its outer membrane. A red blood cell has hardly any of this equipment—a couple of channels for water and other essentials—because oxygen and carbon dioxide can diffuse through its membrane without any help. And while other cells have intricate scaffolding inside their membranes to keep them stiff and strong, a red blood cell is the contortionist of the body’s cellular circus. It travels three hundred miles in its lifetime, blasted and buffeted by the flow of blood, crashing into vessel walls and getting squeezed through slender capillaries, where it has to travel with other red blood cells in single file, compressed to about a fifth of its normal diameter, bouncing back to its normal size once it’s through.
In order to survive the abuse, the red blood cell has a network of proteins undergirding its membrane that are arrayed like the knit of a mesh bag. Each string of proteins making up the mesh is also folded up like a concertina, allowing it to stretch out and squeeze back in response to stress coming from any direction. But as flexible as a red blood cell may be, it can’t take this abuse forever. Over time its membrane becomes stiff, and it has a harder time squeezing through the capillaries. It’s the spleen’s job to keep the body’s blood supply young and vibrant. As red blood cells pass through the spleen it inspects them carefully. It can recognize the signs of old age on the surface of red blood cells, like the wrinkles on a face. Only young red blood cells make it out of the spleen; the rest are destroyed.
Despite all of the disadvantages of a red blood cell, Plasmodium seeks out this strange empty house. The parasites can’t swim, but they can glide along the walls of blood vessels. To do so, they set down hooks on the vessel wall, drag them back to their tail end, and put new hooks down to take their place, like a cellular tank tread. At the parasite’s tip are sensors that respond only to young red blood cells, clasping on to proteins on the cells’ surface. Once Plasmodium fixes on a cell, it latches on and rolls itself over onto its head and prepares to invade.
The head of the parasite is ringed by a set of chambers like the barrel of a revolver. Out of the chambers comes a blitz of molecules in a matter of seconds. Some of the molecules help the parasite push aside the membrane skeleton and work its way inside. The same hooks that acted as the parasite’s tank treads while it wandered along the vessel walls now latch on to the edges of the hole and drive the parasite through it. The parasite blasts out sheets of molecules, which join together and form a shroud around the parasite as it goes in. Fifteen seconds after the blast, Plasmodium’s back end disappears through the hole, and the resilient meshwork of the red blood cell simply bounces back again, sealing itself shut.
Once inside, the parasite is in the pantry. Each red blood cell’s interior is 95 percent hemoglobin. Plasmodium has a mouth of sorts on one side—a port that can swing open—and when it does, the outer membrane of the parasite’s bubble opens as well, bringing the parasite briefly into contact with the red blood cell’s contents. A little dollop of hemoglobin oozes into the maw, which then twists shut. The hemoglobin now floats in a bubble inside the parasite, which contains molecular scalpels that slice apart the molecules. Plasmodium makes a succession of cuts that open up their folded branches, letting them fall apart into smaller pieces and capturing the energy that had been held in those bonds. The core of hemoglobin molecules is a strongly charged, iron-rich compound that is poisonous to the parasite. It tends to lodge itself in Plasmodium’s membrane, where its charge disrupts the normal flow of other molecules in and out. But Plasmodium can neutralize the toxic heart of its meal. It strings some of it in a long, inert molecule called hemozoin. The rest of the compound gets processed by the parasite’s enzymes, which reduce its charge and make it unable to penetrate the membrane.
Plasmodium does not live by hemoglobin alone, however. It needs amino acids to build its molecular scalpels, and it also needs them to multiply into sixteen new copies. In those two days, the metabolic rate within an infected cell rises three hundred fifty times, and the parasite needs to make new proteins and get rid of the wastes that it makes as it grows. If Plasmodium had infected a true cell, it could simply hijack its host’s biochemistry for those jobs, but in a red blood cell it has to build the machinery from scratch. In other words, Plasmodium has to transform these mere corpuscles into proper cells. Out from its bubble it extends a tangled maze of tubes that reach all the way to the membrane of the red blood cell itself. It’s not clear whether Plasmodium’s tubes actually punch their way through the membrane of the red blood cell or jack into the channels that are already there. In either case, the parasitized red blood cell can start dragging in the building blocks the parasite needs to grow.
Suddenly crowded with channels and tubes, the surface of the red blood cell starts to lose its springiness. This could be fatal for the parasite, because if the spleen discovers that the cell is no longer its lithe young self, it will destroy it—along with any parasites it may harbor. As soon as it enters the red blood cell, Plasmodium releases proteins that are ferried through the tubes to the underside of the cell’s membrane. These molecules belong to a common class of proteins found in every sort of organism on Earth. Known as chaperones, they help other proteins fold and unfold properly even when they’re being disrupted by heat or acid. In the case of Plasmodium’s proteins, though, the chaperones seem to protect the red blood cell from the parasite itself. They help the cell’s skeleton stretch out and collapse back tight again, despite the parasitic construction getting in their way.
Within a few hours, the parasite has transformed and stiffened the red blood cell so much that there’s no hope in trying to disguise it as a healthy corpuscle. Now the parasite dispatches a new set of proteins to the surface of the cell. Some of them ball up in clumps under the cell’s surface, giving the membrane a goose-bumpy look.
Plasmodium then pierces the goose bumps with sticky molecules that can grab hold of receptors on the cells of the blood vessel walls. As these red blood cells stick to the vessel walls they drop out of the body’s circulation. Rather than trying to sneak through the slaughterhouse of the spleen, Plasmodium evades it altogether. Their red blood cells instead clump up in capillaries in the brain, the liver, and other organs. Plasmodium spends another day dividing, until the red blood cell is nothing more than a taut skin around the bulging bundle of parasites. Finally, the new generation of Plasmodium breaks out of the cell and looks for new red blood cells to invade. Left behind in the dead cell is a clump of used-up hemoglobin. For a time the cell was the parasite’s home, a cell like none other in the human body, but in the end it becomes its garbage dump.