Studying activation and adaptation of mechanosensory cells in their native context
Abstract:
Mechanosensory cells experience a broad range of forces, but their mechanically-sensitive ion channels, by comparison, have narrow operating ranges. To get around this limitation, and retain broad sensitivity, sensory cells express other molecular players that allow adaptation to impinging forces. Through adaptation, the comparatively narrow range of forces which drive transduction can be more usefully deployed.
We seek greater understanding of how mechanically-sensitive ion-channels, adaptive subcellular processes, and their architectural substrates work together to allow mechanosensation on a cellular level. Moreover, we would like to know how these subcellular processes operate in the broader cytoarchitectural context of sensory organ function.
Overcoming longstanding limitations, we have established a system which enables both precise mechanical stimulus control, and, simultaneously, direct access to sensory cells in their native environment. We accomplish this using the Drosophila antennal mechanosensory organ, where we can directly stimulate the antenna to control the cell’s native mechanical input. With in vivo 2-photon microscopy, we can track cellular structures during stimulation. Importantly, this allows us to establish the biomechanical and subcellular chain-of-events leading to ion-channel activation, following forces from external to intracellular. Additionally, using laser microdissection, we can expose the organ and record single-cell electrical activity with patch-clamp electrophysiology to measure transduction resulting from these forces.
Using these techniques, we find evidence that adaptation may occur through cellular processes altering the forces experienced by mechanically-sensitive ion channels. Further, we are developing a mechanistic understanding of how molecular components operate in concert to transmit forces and mediate adaptation by using channel mutants and genetic knock-down. With this system, we hope to better understand how the mechanics of sensory adaptation place constraints on organ function, and, vice versa, how organ-level mechanics place specific demands on subcellular processes.