May 10, 2019 | David F. Coppedge

Extreme Fine Tuning in Body Cells, Part I

Here are two examples of an ultra-fine balance between function and disease inside the cells of our body’s sensory cells (Part 1 of 2).


We learn in school how sound waves hit the eardrum, and then how 3 tiny hinged bones in the middle ear (the ossicles) transmit the vibrations to the cochlea. This train of transmission converts sound energy to mechanical energy, and then to fluid energy. But that’s not the end of the train. That fluid energy converts the vibrations to electrical energy before it reaches the brain’s hearing center. How? Inside the fluid of the cochlea, miniature “hair cell bundles” open and close ion channels in the auditory neurons. You can think of them as tiny pulleys lifting caps on openings in the neurons, allowing electrical ions to flow in (specifically, doubly-charged calcium, Ca2+). That ion flow starts the electrical train. The tips of these hair bundles have spring-like proteins that give them extreme sensitivity to how much they open and close the ion channels. The extreme sensitivity gives us the amazing ability to hear the faintest sounds (when just a few ions flow in), and the loudest sounds (when many ions flow in) — a trillion-to-one range of dynamics. (The ear also includes automatic quenching mechanisms to prevent loud sounds from damaging the ear, but that’s another story.)

Diagram of the human ear.

How does the tip of the hair bundle achieve its exquisite sensitivity? The springy protein cannot be too stiff, or too loose. It needs, like Goldilocks’ soup, to be ‘just right.’ Scientists writing in the Proceedings of the National Academy of Sciences (PNAS) found that a protein named protocadherin 15 is the fine tuner. In their paper, “Elasticity of individual protocadherin 15 molecules implicates tip links as the gating springs for hearing,” they describe this delicate balance:

Our hearing depends on mechanosensitive channels in hair cells of the inner ear. Experiments suggest that each channel is opened by a “gating spring,” an elastic element that conveys displacement of a hair bundle to the channel. Appropriate stiffness of the gating spring permits the discrimination of different sound amplitudes; if the spring is too stiff, then a faint sound will elicit the same response as a loud sound, opening all of a cell’s channels. Although the tip link—a fine molecular filament—might be the gating spring, its properties have remained controversial. Using high-precision optical tweezers, we demonstrate that the mechanical properties of a tip link protein correlate with those of a gating spring in vivo [in life].

In addition to the properties of protocadherin 15, the authors say that “tip link tension and Ca2+ concentration are likely parameters through which nature tunes a gating spring’s mechanical properties.” This fine-tuning gives us humans the dynamic richness to enjoy music, speech and all the sounds of nature. We should remember, though, that the same mechanisms work in guinea pigs, bullfrogs, dolphins, and every animal with similar hearing systems.

Tomorrow we will look at another case of extreme fine-tuning in the body. Don’t miss it!

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