A Photostable Silicon Rhodamine Platform for Optical Voltage Sensing

Area of Science:

• Neuroscience
• Biophysics
• Materials Science

Background:

• Optical voltage sensing is crucial for understanding neuronal function.
• Existing voltage sensors often lack photostability or optimal spectral properties for advanced applications.
• Far-red to near-infrared (NIR) probes are desirable for reduced phototoxicity and deeper tissue penetration.

Purpose of the Study:

• To design and synthesize a photostable, far-red to NIR voltage-sensitive fluorescent probe.
• To develop a new class of voltage sensors utilizing a photoinduced electron transfer (PeT) mechanism.
• To demonstrate the utility of the new probe in living cells and neurons for optical electrophysiology.

Main Methods:

• Synthesis of a novel sulfonated silicon rhodamine fluorophore integrated with a phenylenevinylene molecular wire.
• Development of the Berkeley Red Sensor of Transmembrane potential (BeRST 1) probe.
• Characterization of BeRST 1's fluorescence, photostability, and voltage sensitivity in living cells and primary neurons.

Main Results:

• BeRST 1 exhibits bright, membrane-localized fluorescence in living cells.
• The probe demonstrates high photostability and excellent voltage sensitivity (24% ΔF/F per 100 mV depolarization).
• BeRST 1 is compatible with other cellular imaging techniques and optogenetic tools.

Conclusions:

• BeRST 1 represents a significant advancement in optical voltage sensing technology.
• Its unique spectral properties and performance characteristics enable noninvasive optical dissection of neuronal activity.
• This platform facilitates optical electrophysiology, particularly in conjunction with optogenetic actuators requiring different light spectra.