The mechanical control of the sense of touch

Forces are a ubiquitous challenge to all cells of our body and a protective mechanism has to be present. Some of the cells in our body have specifically evolved to detect these forces and convert mechanical energy into electrical signals that elicit an appropriate behavior. How they are able to withstand such mechanical insult without physical damage, while remaining sensitive enough to the stimulus to sense it, is not fully understood. Using the touch receptor neurons (TRNs) of C elegans as a model system, we showed that a mechanically pre-stressed spectrin cytoskeleton is important for both shape stability and sensation of mechanical forces.

HFSP Long-Term Fellow Michael Krieg and colleagues
authored on Fri, 25 April 2014

To analyse how the neuron complies to muscle generated forces, we imaged TRN shape when the animal is moving using a confocal microscope. To our surprise, the neurons behaved like an elastic spring, continuously extending  and shortening, as the animal bent its body exerting either tensile or compressive forces onto it. We then investigated the molecular origin of the spring and reasoned, that if we were able to soften or destroy the spring, the shape of the neuron would be altered.  Consistent with this idea, we found that the neuron loses its ability to respond to body-evoked forces and deforms under compressive forces in animals lacking a functional spectrin network. The neuron starts to collapse, reminiscent of a buckling instability. We then reasoned that the spectrin cytoskeleton might increase the resilience of the neuron to mechanical stress by augmenting mechanical tension within their neurites. To test this possibility, we used atomic force microscopy to measure the force needed to deform the membrane-bilayer in wildtype and spectrin mutant TRNs and found that spectrin mutant cells are less resistant to deformation than control cells. To visualize mechanical tension of the neuron within the animal, we cut the neurite and observed the severed ends directly after axotomy. Consistent with our previous observation and our hypothesis, the neurite retracted with high velocity in control cells, but not in neurites lacking a functional spectrin network. Finally, with the help of genetically encoded stress-sensors, we showed that spectrin is held under a constitutive tension of about 1pN in the living animal.

Figure: Two spectrin mutant animals with a point defect in the tetramerization domain show a buckling defect in their touch receptor neurons when subjected to compressive forces.   The TRNs which are not subjected to compressive forces remain straight.

But what is the benefit of having a prestressed cytoskeleton within TRNs? Think of the kid's game in which two empty aluminum cans are connected by a cord. If the cord is taut, you can communicate and talk to each other over a long distance, just as if it was a telephone. That’s a mechanical system for information exchange. In the neuron, the can receiving the mechanical signal is a mechanosensitive ion channel, and we know that pre-stressing of the neurons by spectrin helps the neuron respond to that signal. But how the information actually reaches the mechanosensitive ion channel is still an unresolved mystery.

Reference

Mechanical control of the sense of touch by β-spectrin. Krieg M, Dunn AR, Goodman MB. Nat Cell Biol. 2014 Mar;16(3):224-33. doi: 10.1038/ncb2915. Epub 2014 Feb 23.

Pubmed link