Scientists identify molecular cause for
one form of deafness
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[February 26, 2007]
-- Scientists exploring the physics of hearing have found an
underlying molecular cause for one form of deafness, and a
conceptual connection between deafness and the organization of
liquid crystals, which are used in flat-panel displays.
Within the cochlea of the inner ear, sound waves cause the basilar
membrane to vibrate. These vibrations stimulate hair cells, which
then trigger nerve impulses that are transmitted to the brain.
Researchers have now learned that mutations in a protein called
espin can cause floppiness in tiny bundles of protein filaments
within the hair cells, impairing the passage of vibrations and
resulting in deafness.
Filamentous actin (F-actin) is a rodlike protein that provides
structural framework in living cells. F-actin is organized into
bundles by espin, a linker protein found in sensory cells, including
cochlear hair cells. Genetic mutations in espin's F-actin binding
sites are linked to deafness in mice and humans.
"We found the structure of the bundles changes dramatically when
normal espin is replaced with espin mutants that cause deafness,"
said Gerard Wong, a professor of materials science and engineering,
of physics, and of bioengineering at the University of Illinois at
"The interior structure of the bundles changes from a rigid,
hexagonal array of uniformly twisted filaments, to a liquid
crystalline arrangement of filaments," Wong said. "Because the new
organization causes the bundles to be more than a thousand times
floppier, they cannot respond to sound in the same way. The rigidity
of these bundles is essential for hearing."
Wong and his co-authors -- Illinois postdoctoral research
associate Kirstin Purdy and Northwestern University professor of
cell and molecular biology James R. Bartles -- report their findings
in a paper accepted for publication in the journal Physical Review
Letters, and posted on the Web.
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High-resolution X-ray diffraction experiments performed by Purdy at
the Advanced Photon Source and at the Stanford Synchrotron Radiation
Laboratory allowed the researchers to solve the structure of various
"As the ability of espin to cross-link F-actin is decreased by
using genetically modified 'deafness' mutants with progressively
more damaged actin-binding sites, the structure changes from a
well-ordered crystalline array of filaments to a nematic, liquid
crystal-like state," said Wong, who also is a researcher at the
Frederick Seitz Materials Research Laboratory on campus and at the
university's Beckman Institute for Advanced Science and Technology.
In the liquid crystalline state, the bundles maintain their
orientation order -- that is, they point roughly along the same
direction -- but lose their positional order. These nematic liquid
crystals are commonly used in watch displays and laptop displays.
Wong and his colleagues also found that a mixture of mutant espin
and normal espin would prevent the structural transition from
occurring. If gene expression could turn on the production of just a
fraction of normal espin linkers, a kind of rescue attempt at
restoring hearing could, in principle, be made.
"We have identified the underlying molecular cause for one form
of deafness, and we have identified a mechanism to potentially
'rescue' this particular kind of pathology," Wong said. "Even so,
this is really the first step. This work has relevance to not just
human hearing, but also to artificial sensors."
The U.S. Department of Energy, National Institutes of Health and
National Science Foundation funded the work.
[Text copied from
University of Illinois at Urbana-Champaign News Bureau release]