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Membrane potential sensing: Material design and method development for single particle optical electrophysiology.

Debjit Roy1, Zehavit Shapira2, Shimon Weiss1

  • 1Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California 90095, USA.

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Single nanoparticle voltage sensors offer a non-genetic optogenetics tool. Inorganic and organic sensors use optical imaging for fast, high-resolution membrane potential detection in cells.

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Area of Science:

  • Nanotechnology and Biophysics
  • Optical Imaging and Sensing

Background:

  • Development of voltage sensors is crucial for understanding cellular electrophysiology.
  • Non-genetic optogenetics offers an alternative to traditional genetic methods for controlling cellular activity.
  • Single nanoparticle-based sensors provide high spatial and temporal resolution for voltage sensing.

Purpose of the Study:

  • To review the development of inorganic and organic nanoparticle-based voltage sensors.
  • To explore their potential as tools for non-genetic optogenetics.
  • To evaluate their performance in sensing membrane potential changes.

Main Methods:

  • Inorganic sensors utilize the Quantum Confined Stark Effect (QCSE) for electric field detection.
  • Organic sensors employ Förster Resonance Energy Transfer (FRET) for voltage sensing.
  • Both sensor types are evaluated using fluorescence microscopy on cell cultures (HEK293, neurons).

Main Results:

  • Engineered inorganic nanoparticles show high single-particle voltage sensitivity (∼30% ΔF/F per 160 mV).
  • Hybrid nanobiomaterials enable effective cellular compartmentalization and detection of membrane potential (MP) changes.
  • Organic FRET-based sensors achieve up to 35% ΔF/F per 120 mV sensitivity, enabling non-invasive recording from targeted sites like synapses.

Conclusions:

  • Nanoparticle-based voltage sensors are emerging as viable tools for non-genetic optogenetics.
  • Current QCSE and FRET sensors demonstrate significant voltage sensitivity and potential for cellular imaging.
  • Further development is needed to record individual action potentials from targeted cellular sites.