Tuning PIEZO ion channels to detect molecular-scale movements relevant for fine touch

C Wetzel1, JH Stear1,2, M Moroni1, GR Lewin1 and K Poole1,2

  1. Max Delbruck Center for Molecular Medicine
  2. School of Medical Sciences, University of New South Wales

The conversion of mechanical inputs into an electrical signal in somatosensory neurons is essential for our sense of touch. Mechanically-gated ion channels, such as the PIEZO channels, mediate this signal transduction process, largely within the cell-matrix interface. A unique aspect of mechanical activation of ion channels, in comparison to other gating mechanisms, is that the applied physical stimulus will be modulated by all of the physical elements in the pathway from the site of stimulus application to the channel itself. As such, it is important to understand how accessory proteins (both extracellular and intracellular) can locally regulate mechanosensitive channel activation, within transmembrane force-sensing domains. In order to quantitatively study mechanosensitive channel activity we are utilising a method to directly monitor mechanoelectrical transduction at defined regions of the cell-substrate interface. We have found that molecular-scale (approx. 13 nm) displacements are sufficient to gate mechanosensitive currents in mouse, touch receptive neurons. Such sensitive responses are dependent on the membrane scaffolding protein, STOML3 and the underlying extracellular matrix. We have been investigating how the patterning of these molecules within the cell-matrix interface relates to the molecular-scale sensitivity of somatosensory neurons.