|M.Sc Student||Friman Itai|
|Subject||Modeling Sound Sensing and Transduction in the Outer Hair|
Cell in the Mammalian Hearing System
|Department||Department of Biomedical Engineering||Supervisor||PROFESSOR EMERITUS Eitan Kimmel|
|Full Thesis text|
_ The outer hair cells are an array of organized cells located in the organ of Corti in the spiral Cochlea in the inner ear of mammals. They are, possibly, the main element of the cochlear active amplifier, a mechanism experimentally proven to have a critical importance to the sound signal processing in the ear. It is known that the outer hair cells are mechanically coupled with the basilar membrane and the tectorial membrane through the stereocilia, yet the exact process is not fully understood. However, it is widely thought that this structure is the key for auditory unique capabilities of the inner ear.
A new model focusing on the outer hair cell has been developed recently. The model predicts that the outer side of the lateral wall of the outer hair cell is composed of many units (~105 -106) called nanometric acoustic motile sensors. Each unit is a piece of plasma membrane that hops randomly between two pseudo-stable states because of thermal fluctuations. Upon exposure of the outer hair cell to a signal of its respective frequency, the nanometric acoustic motile sensors exhibit synchronized movement. Furthermore, these units are embedded with prestin, a motor protein which is suggested to modulate the surface area of the plasma membrane by its contraction and relaxation. This induces temporal spikes of tension in the lateral wall, allowing transduction of an acoustic pressure wave into an axial force applied on both the tectorial membrane (through the stereocilia) and the basilar membrane, giving the outer hair cell its sound motility.
In this study, an elaboration of the aforementioned model is suggested to account for voltage clamp experiments in an excised outer hair cell that reveal electromechanical coupling by cellular length changes as well as nonlinear capacitance, and link these observations to the prestin operation. The prestin is assumed to: [i] be an allosteric modulator operating by an electric interaction with adjacent ions; [ii] roll inside the plasma membrane, and thus change its surface area.
The nanometric acoustic motile sensors functioning was simulated to describe outer hair cell length changes under the influence of the membrane charge. Furthermore, a theoretical relationship between the unit states and the outer hair cell electromotility was developed to estimate the effect of the induced charge on the cell modulation. As commonly used in small system dynamics, fundamentals of statistical physics were employed and poured to a harmonic oscillator and a two-state conceptual model of the sensors.
It was demonstrated that the prestin on the units electrically interacts with spectrin protein. The strength of the interaction expresses the responsivity of the units to acoustic pressure waves and is controlled by predicted induced charges derived from the membrane potential.
The electromechanical coupling demonstrated here addresses the model of the sensor units for the outer hair cell role as both a transducer and a sensor in the hearing system, and suggests a possible explanation of the cell modulation by the brain through efferent nerves.