Understanding sensory nerve mechanotransduction through localized elastomeric matrix control.
BACKGROUND
While neural systems are known to respond to chemical and electrical stimulation, the effect of mechanics on these highly sensitive cells is still not well understood. The ability to examine the effects of mechanics on these cells is limited by existing approaches, although their overall response is intimately tied to cell-matrix interactions. Here, we offer a novel method, which we used to investigate stretch-activated mechanotransduction on nerve terminals of sensory neurons through an elastomeric interface.


RESULTS
To apply mechanical force on neurites, we cultured dorsal root ganglion neurons on an elastic substrate, polydimethylsiloxane (PDMS), coated with extracellular matrices (ECM). We then implemented a controlled indentation scheme using a glass pipette to mechanically stimulate individual neurites that were adjacent to the pipette. We used whole-cell patch clamping to record the stretch-activated action potentials on the soma of the single neurites to determine the mechanotransduction-based response. When we imposed specific mechanical force through the ECM, we noted a significant neuronal action potential response. Furthermore, because the mechanotransduction cascade is known to be directly affected by the cytoskeleton, we investigated the cell structure and its effects. When we disrupted microtubules and actin filaments with nocodozale or cytochalasin-D, respectively, the mechanically induced action potential was abrogated. In contrast, when using blockers of channels such as TRP, ASIC, and stretch-activated channels while mechanically stimulating the cells, we observed almost no change in action potential signalling when compared with mechanical activation of unmodified cells.


CONCLUSIONS
These results suggest that sensory nerve terminals have a specific mechanosensitive response that is related to cell architecture.
Lin
Yi-Wen
YW
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Cheng
Chao-Min
CM
Leduc
Philip R
PR
Chen
Chih-Cheng
CC
D000200:Action Potentials / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D004129:Dimethylpolysiloxanes / Q000378:metabolism*; D004548:Elasticity / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D049990:Membrane Transport Modulators / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D013314:Stress, Mechanical
D004129:Dimethylpolysiloxanes; D049990:Membrane Transport Modulators