What is the Molecular Basis of the Robust Architecture of Hair Cells?

hair cells are sensory receptors that convert mechanical stimuli, such as sound or head movements, into electrical signals the brain can interpret; this process is known as mechanotransduction.

Hair cells and Stereocilia

hair cells feature stereocilia–actin-rich microvilli that extend from their apical surface–on their apical surface. Stretching the cell causes these stereocilia to deflect under mechanical strain and, in doing so, opens mechanically gated ion channels that admit positively charged ions such as potassium and calcium into their interiors.

Maintenance of Stereocilia

Mammals depend on stereocilia bundles projecting from their organ of Corti, yet these structures do not regenerate even with sound exposure. Stereocilia contain actin cores consisting of tightly packed, parallel filaments crosslinked by stable proteins. Multiple techniques have demonstrated the stability of these proteins over time.

Stereocilia cores are controlled by several classes of binding proteins, with myosin motor proteins such as gelsolin, fascin-2, and EPS8L2 playing a prominent role in maintaining stereocilia stability and lengthening. Loss of these myosin motor proteins causes selective disassembly of short rows of stereocilia.

Actin severing protein ADF could encourage stereocilia lengthening or turnover by antagonizing the capping of barbed end filament monomers.

Mechanical deflection of hair cells’ stereocilia triggers electro-mechanical transduction. Tip links, stretch-sensitive extracellular filaments, connect each stereocilium to its tallest neighbor along the axis of mechanical sensitivity. Tip links open ion channels under stress but close upon stimulation, allowing excitation.

High-resolution TEM images reveal that tip link proteins possess an undulated buckled structure without sharp bends, suggesting high flexural rigidity. These proteins bind strongly at rest but quickly rebind under constant force.

Electro-Mechanical Transduction

Mammalian cochleas achieve high-frequency resolution through active mechanical amplification by outer hair cells. Mechanotransduction refers to the process by which mechanical input activates ion channels in sensory cells, changing their membrane potential and relaying the message to the brain.

Integral polymer MEMS offer an appealing alternative to silicon-based sensors for strain sensing applications. Implementing an organic field effect transistor embedded within an SU-8 polymeric cantilever operating in static mode has been suggested.

Nerve Terminals and Synaptic Transmission

Axons conduct action potentials to synapses for synaptic transmission. Their terminal contains chemicals like acetylcholine that are released when hair cells become active.

Endolymph surrounding hair cells is rich in potassium and electrically positive relative to their interiors. When potassium enters through channels, it opens voltage-gated calcium channels on hair cells, depolarizing and increasing the release of glutamate neurotransmitters.

Nerve fibers densely innervate inner and outer hair cell nerve fibers, but the input patterns differ. One inner hair cell receives input from multiple nerve fibers, while numerous outer hair cells receive information from only one nerve fiber.