Sleuthing in the Cellular World: Sheldon Weinbaum's Biomedical Research
"My nose is always out to smell a mystery," says Sheldon Weinbaum from behind his desk in the City College Department of Engineering. Although he doesn't solve crimes, investigate UFO sightings, or perform high-tech autopsies, Weinbaum--a CUNY Distinguished Professor on the faculty of the Ph.D. Program in Engineering--does play the role of a detective. He cracks cases that have baffled scientists for centuries, concerning the mechanics of the human body at the cellular level. "I think of these things as physiological mysteries about how the cells of our bodies function," he says.
Here's one for you. How is it that red blood cells can repeatedly pass through blood vessel openings that are smaller than they are, without becoming damaged? How do they live so long? A red blood cell is about eight microns in diameter, but it fits through capillary openings of only five or six microns in diameter without showing any wear and tear. It manages this tight squeeze about 100,000 times in its lifetime before apoptosis (or, natural cell death), and yet it has a fragile membrane, says Weinbaum. "How could there be so little friction?" he asks.
The answer lies in an insight Weinbaum had one winter day in Minnesota, standing in the extreme cold, with snow on the ground. "I came up with this theory that red blood cells were basically the world's best skiers," he says. The lining of the blood vessels is covered with something called the glycocalyx--a coat of glycoproteins, or sugars, which, Weinbaum surmised, functions essentially like snow under a pair of skis. He hypothesized that, when the red blood cell was moving, even very slowly, there would be a small cushion between its membrane and that of the endothelial cells of the blood vessel. But when the red blood cell came to rest, the two membranes would be virtually touching. "You know how when you stand in a fresh snow, you can crush it entirely?" he asks. "So I started thinking, the glycocalyx is like snow."
Like any good sleuth, Weinbaum knows a good lead when he sees one. He had to check it out. He came back to New York and hired a ski instructor to go with him up to Hunter Mountain. There had been a ten-inch snow fall. Weinbaum sent the ski instructor down the mountain and then measured the depths of his tracks, which only five inches while moving. However, when the skier simply stood still in his tracks, he would sink all the way down to the ground.
"Skiers will tell you that they feel like they are riding on air," says Weinbaum, and this is actually true--air gets trapped in the compressed snow under the skis and can't escape fast enough, so it creates a lift force or pressure against the skier's weight. The same physical dynamics are at work with a red blood cell--the pressure due to fluid trapped in the glycocalyx lifts the cell away from the capillary wall during the time that it is in motion. The hunch that Weinbaum had in the Minnesota winter became an important insight for studying the mechanics of red blood cells, and not only by providing a good analogy: Weinbaum found that, quantitatively, the governing equations that describe a red blood cell floating on the glycocalyx are almost identical to those describing the mechanics of skiing. "This was almost beyond imagination," says Weinbaum. "For this similarity to occur across so many orders of mass is truly unbelievable." However, there is one difference. A red blood cell moves with a velocity of about fifty times its length per second, whereas the fastest skier can go only about thirty times his or her length in a second.
"So you could never be as good a skier as a red blood cell," he says. The reason: air escapes around the lateral edges of a skier's skis, causing a loss of the supporting pressure, but a blood cell moves through a capillary that entirely surrounds it, so there are no lateral edges through which the trapped fluid can escape and cause the pressure to relax.
Case closed.
According to Weinbaum, his ability to solve age-old conundrums of cellular motion relies on a kind of "sixth sense" or "a physical intuition" that he has developed over his 35-year career at City
College, where he was instrumental in establishing the New York Center for Biomedical Engineering, which he directed from 1994 to 1999. He is chair of the new biomedical engineering department at City College, and he initiated the proposal for biomedical engineer
ing in The Graduate Center's Ph.D. Program in Engineering. Weinbaum's success involves "having these whimsical ideas that explain
what you would think of as very strange things," he says.
Weinbaum--one of only eight living scientist to be elected to the triumvirate of the National Academy of Science, the National Academy of Engineering, and the National Academy of Medicine--has used his unorthodox methods to unravel a series of biomedical paradoxes. To name a few: he discovered the pore that allows LDL cholesterol to enter the endothelial (blood vessel) lining; he developed, with his City College and Graduate Center colleague, Latif Jiji, a governing equation for heat transfer in micro-circulation (known as the Weinbaum-Jiji Bioheat Equation); and, in 1994, he published a paper with CUNY Distinguished Professor Stephen Cowin that started a new field of research on bone fluid flow (investigating how it is that bone cells--whose movements are barely measurable--can sense when they are being subjected to external stress).
"I'm a theoretician, a model maker," says Weinbaum, who claims that he has never done an experiment. Instead, he must rely on experimental collaborators--esteemed researchers in a variety of disciplines--to put his theories into practice. "Nobody believes just a theory," he says, "so everything I do has to be proven by other people." Whereas most engineers have a single specialty, he is a jack of all trades, a scholar who works best by letting his creativity range across multiple problems and perplexities.
Here's another one. How is it that white blood cells, which have about twenty-five prong-like feet (or microvilli) in a cross-section, can move across the glycocalyx without slowing down--without getting their feet stuck in the 'snow'? Weinbaum's answer to this brain-teaser was like something out of Ripley's Believe It or Not: white blood cells are like the Jesus Christ Lizard of Costa Rica, an animal that can walk on water by running incredibly fast. "Every time its foot hits the water, there is a reaction force," says Weinbaum. If this occurred frequently enough, then the white blood cell, like the lizard, wouldn't sink in, he guessed. And he was right. This insight, too, was proven in experiments to be correct.
Just another day on the job for Sheldon Weinbaum, ace detective of the cellular world.
