New studies in hearing loss are increasing steadily, and the scientific world in scrambling to understand, and hopefully come up with some answers to the effects of man made noise on human hearing.
One researcher - Manfred Auer of Berkeley Lab’s Life Sciences Division - caught my eye with this succinct comment: "Finding a way to regenerate hair cells is the Holy Grail of research; We're born with just 16,000 hair cells in the cochlea, and every passing subway train kills a few of them."
Finding a way to regenerate the delicate inner ear hair cells is work Auer and other researchers are dedicating large chunks of time and resources to, as the industrialed world suffers greater degrees of hearing loss each year.
IIOne out of a thousand children in the United States is born IIdeaf; ten percent of all people living in industrialized nations IIsuffer from severe hearing loss — 30 million in the U.S. alone. IIThese are pressing clinical reasons to learn just how hearing IIworks and why it fails.
II"Hearing in humans is a remarkable faculty," says Auer "It works IIover six orders of magnitude, from a whisper to the roar of a IIjjet engine. If it were just a little more sensitive, we'd be able IIto hear the atoms colliding with our eardrums — in other IIwords, our hearing is about as sensitive as we can stand IIwithout going crazy."
IIHearing is also remarkable for its ability to adapt to constant IIloud noise yet still manage to pick out barely distinguishable sounds, "like being able to follow a single conversation across the room at a cocktail party, or hearing someone shout at you over the noise of a rock band," says Auer.
And humans can pinpoint the source of a sound to within less than a degree: one ear hears the sound slightly before the other, and the brain calculates the direction from the offset. But the difference in arrival times is less than a millionth of a second, a thousand times faster than most biochemical processes; thus hearing must depend on direct mechanical detection of sounds instantly translated into nerve signals.
The inner ear's hair cells are the key. They convert mechanical responses into electrical signals that trigger adjacent neurons in the brain — a prime example of a phenomenon, fundamental in tissue and cell biology, known as mechanosensation. Hair cells are embedded in the epithelial lining of the cochlea, where they respond mechanically to sound vibrations; others in the nearby vestibular labyrinth move in response to radial and linear acceleration and are the source of the sense of balance.
Thus beyond practical concerns lie basic scientific questions about the exact molecular composition and three-dimensional architecture of hair cells and related entities. A uniquely powerful tool for exploring biological structures at this subcellular but supramolecular level is electron microscope tomography — electron tomography for short.
A Hairdo for Hearing
The part of the hair cell that mechanically responds to vibration (or acceleration) is a bundle of fibers called stereocilia, sticking out of the top of the cell like a radical hairdo. In zebrafish the stereocilia are arranged in stair-step fashion. The tallest shaft, made of bundles of cylindrical microtubules, acts like a tent pole to support the development of all the others, which are made of bundles of the protein actin. Each actin-based fiber is shorter than the one next to it, and the tip of each lower fiber is attached diagonally to the side of the adjacent taller fiber by a fine filament called a tip link.
When vibration pushes against the bundle of stereocilia the fibers lean over, stretching the tip-link filaments. This pulls open nearby channels in the fibers (one or two per fiber), allowing potassium ions to flow into the fiber and down to the body of the cell. The electrical balance between calcium and potassium ions in the cell is instantly changed, triggering a signal to adjacent neurons.
If the hair bundle remains bent by persistent noise, a higher level of calcium in the cell signals the structural protein myosin, also present in the stereocilia, to slide down along the actin fibers. By resetting the tension on the tip-link springs in this way, hair cells can adapt to sustained noise levels.
"There are two ways hearing can be damaged by loud noises," Auer says. "Noise can stress the stereocilia bundle so much that the tip links break. However they usually grow back in 24 hours — this is the rock-concert effect, where hearing loss is temporary. But loud noises can also shear off whole bundles of stereocilia. In mammals these can't regenerate, and the loss is permanent."
Finding a way to regenerate hair cells, says Auer, "is the Holy Grail of research. We're born with just 16,000 hair cells in the cochlea, and every passing subway train kills a few of them."
Taken individually, the images of stereocilia from which Auer and his colleagues construct electron tomographs don't look much different from the many other microscopic studies of these structures — including blobs near the tips of the fibers that researchers customarily dismissed as "dirt." But, says Auer, "We think there is no such thing as dirt."
Because electron tomography allows "dissection in silico" Auer's group has been able to analyze these mysterious artifacts, giving rise to provocative hints of unsuspected tip-link structures — including whether there may be more than a single tip link between fibers, how tip links are structured, and what protein or proteins constitute the tip links.
"Until lately, the only protein firmly associated with stereocilia tip structures besides actin was myosin. Now we have 50 candidates — all because we could look at that 'dirt' in 3-D." Auer and his collaborators have developed good evidence for just which proteins are involved in tip-links and in other links among stereocilia. They plan to publish their findings soon.
And That's Just the Beginning
"For years, because they have understandably concentrated on disease organisms, microbiologists ignored the most basic condition of bacterial life, which is that bacteria live in communities," Auer says. Already electron tomography studies have revealed fascinating and unsuspected features of the bacterial communities known as biofilms. Contrary to what most biologists have thought, some biofilms — supposedly made up of independent bacterial cells — have many of the hallmarks of organized tissues.
Indeed, Auer says, "a biofilm is a prokaryotic version of a tissue," and he plans to publish research results soon, demonstrating these similarities in startling detail.
Because electron tomography can bridge the gap between ultrahigh-resolution protein structures and the large-scale organization of cells and tissues available to the light microscope, Auer says, "I would contend that electron tomography will play a major role in investigating all aspects of biology — in structural biology, cell biology, proteomics, biochemistry, physiology, pathology, evolution, everything. Once you have this new toy, you can apply it to all these questions."