Ultrasonic Control of Neural Activity through Activation of the Mechanosensitive Channel MscL

Nano Lett. 2018 Jul 11;18(7):4148-4155. doi: 10.1021/acs.nanolett.8b00935. Epub 2018 Jun 19.


Externally controlling the excitation of a neuronal subset through ion channels activation can modulate the firing pattern of an entire neural circuit in vivo. As nanovalves in the cell membrane, ion channels can be opened by light (optogenetics) or ultrasonic (sonogenetics) means. A thoroughly analyzed force sensor is the Escherichia coli mechano sensitive channel of large conductance (MscL). Here we expressed MscL in rat hippocampal neurons in a primary culture and showed that it could be activated by low-pressure ultrasound pulses. The gain-of-function mutation, I92L, sensitized MscL's sonic response, triggering action potentials at a peak negative pressure as low as 0.25 MPa. Further, the I92L MscL reliably elicited individual spikes by timed brief pulses, making excitation programmable. Because MscL opens to tension in the lipid bilayer, requiring no other proteins or ligands, it could be developed into a general noninvasive sonogenetic tool to manipulate the activities of neurons or other cells and potential nanodevices.

Keywords: Mechanosensitive channel; MscL; nanovalve; neuron; ultrasound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Biomechanical Phenomena
  • Cell Membrane / chemistry
  • Cell Membrane / genetics*
  • Escherichia coli / chemistry
  • Escherichia coli / genetics
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Gene Expression Regulation / genetics
  • Hippocampus / metabolism
  • Ion Channels / chemistry*
  • Ion Channels / genetics
  • Lipid Bilayers / metabolism
  • Neurons / metabolism*
  • Neurons / pathology
  • Primary Cell Culture
  • Rats
  • Ultrasonics


  • Escherichia coli Proteins
  • Ion Channels
  • Lipid Bilayers
  • MscL protein, E coli