Mystery of Sense of Touch Is within Scientist's Reach

Photograph: Martin Chalfie, professor of biological sciences, has developed the first molecular model to offer an explanation of the sense of touch. Photo Credit: Joe Pineiro.

By Bob Nelson

How do you feel? A Columbia biologist is looking for the precise answer to that question in the cellular structures of the body.

Scientists already know how we see. But how we feel is not well understood. Martin Chalfie, professor of biological sciences at Columbia, has developed the first molecular model to offer a explanation of the sense of touch. The model, which draws on experiments in microscopic roundworms, describes what scientists call a mechanotransduction apparatus, a way for mechanical contact to be translated into sensation.

Senses that allow us to interpret the outside world are based on cellular reception of various external stimuli, such as radiant energy (light) and various chemicals (odors). The sense of sight occurs when light stimulates sensory cells in the retina called rods and cones, which transmit information to the optic nerve.

Translation of a mechanical stimulus into a nerve impulse to the brain, which scientists call mechanosensation, is vital not only to the sense of touch but to hearing and balance as well. "This is a major type of stimulus for which no molecular receptor has been identified in animals," Chalfie said. "This work offers a start in that direction."

Chalfie proposes that mechanotransduction channels on the surface of cells is key to the process. The channels are held in place by proteins, including collagen, on the outside of the cell, and are tethered to a network of microtubules, minute cylindrical structures, within the cell. As the cell is jarred, the microtubules tug on the channel, distorting it and allowing charged ions to move into the cell. The ions depolarize the cell, setting up an electrical stimulus that is eventually passed on to nerve cells and the brain. Since the microtubules are linked together in a network, any disturbance to them could open several channels at once.

The exact chemistry of the process--what ions flow through the channel and which proteins interact and how they create an electrochemical response--is still being investigated, the Columbia biologist said.

Chalfie's research team conducted their experiments in Caenorhabditis elegans, microscopic roundworms with rudimentary nervous systems. The worms responded to a gentle touch, which the researchers applied with an eyebrow hair glued to the end of a toothpick, by moving in the opposite direction. The team bred worms that moved normally but did not respond to the eyebrow hair; touch cells in some of these animals swelled and died, a result the Columbia biologists believe came about because the channels in those mutant cells were held open, causing a continuous influx of ions.

The experiments with mutants have allowed the scientists to pinpoint a series of 12 genes, dubbed mec for mechanosensory, whose products interact to build the various elements of cellular sensing apparatus--channel, extracellular proteins, microtubules--or that produce proteins to regulate the process. The Columbia scientists have cloned and fully described seven of the genes and have partially described one more. They are investigating whether a similar process may be at work in humans and other mammals.

Chalfie has reported various aspects of the work in several journals, most recently the June 1996 issue of the Proceedings of the National Academy of Sciences, along with Guy A. Caldwell, postdoctoral research scientist, and graduate student Guoqiang Gu, both at Columbia. The research was supported by the National Institutes of Health.

Columbia University Record -- November 15, 1996 -- Vol. 22, No. 9