Bioengineering Seminar Spring 2021:Experimental and theoretical investigation of cochlear hair-cell mechanotransduction

Andrei Kozlov, Assistant Professor Department of Bioengineering, Imperial College London
Andrei Kozlov
Department of Bioengineering
Imperial College London
Hair cells, the receptors of the inner ear, detect sounds by transducing mechanical vibrations into electrical signals. From the top surface of each hair cell protrudes a mechanical antenna, the hair bundle, which the cell uses to detect and amplify auditory stimuli, thus sharpening frequency selectivity and providing a broad dynamic range. Current methods for mechanically stimulating hair bundles are too slow to encompass the frequency range of mammalian hearing and are plagued by inconsistencies.
To overcome these challenges, we have developed a method to move individual hair bundles with photonic force. This technique—which relies on the same physical principle that causes a comet’s tail to bend away from the Sun—uses an optical fiber whose tip is tapered to a diameter of a few micrometers and endowed with a ball lens to minimize divergence of the light beam.
Because the “vibrating tool” with which we move a hair cell is a beam of light, our stimulation method is very rapid indeed. It is not limited by the viscous drag on a stimulus fiber or the inertia of a piezoelectric actuator. It is the first method that has no intrinsic frequency limitation. This property alone—and it is not the only one—confers a huge advantage over all existing methods of stimulation.
Powerful experimental tools alone, however, do not guarantee understanding. An appropriate theoretical framework for data interpretation and prediction is just as important. Since the standard theoretical framework in the field, the classical gating spring model developed in the 1980s, has been unable to account for a growing number of experimental results, we have developed a new theoretical model of hair-cell mechanotransduction. Hearing in our model relies on cooperative gating of mechanosensitive ion channels coupled by elastic forces in the lipid bilayer.
In this talk, I will describe both our new experimental method and the theoretical model that reproduces the main biophysical properties of the mechano-electrical transduction using only realistic parameters constrained by experimental evidence.