Membrane-targeted push-pull azobenzenes for the optical modulation of membrane potential

Area of Science:

• Biophysics
• Cellular Electrophysiology
• Photopharmacology

Background:

• Cell stimulation often requires genetic modification or invasive methods.
• Developing non-invasive tools for precise cellular control is crucial for research and therapy.

Purpose of the Study:

• Introduce a novel family of membrane-targeted azobenzenes (MTs) as light-activatable tools for cell stimulation.
• Investigate the mechanism of MT-induced cellular response, focusing on membrane potential modulation.
• Explore the potential applications of MTs in various cell types and physiological contexts.

Main Methods:

• Synthesis and characterization of water-soluble, push-pull azobenzene molecules (MTs).
• Time-resolved spectroscopy and Molecular Dynamics simulations to study photoisomerization and membrane interaction.
• Electrophysiological recordings (membrane potential) in response to light stimulation in HEK293T cells, primary neurons, and cardiomyocytes.

Main Results:

• MTs spontaneously partition into cell membranes and induce reproducible depolarization upon light irradiation.
• Photoisomerization of MTs alters local charge distribution, modulating membrane surface charge and potential.
• MTP2, a key species, demonstrated stable membrane integration and consistent depolarization across tested cell types without altering bilayer thickness.

Conclusions:

• MTs offer a non-invasive, light-controlled method for modulating cell membrane potential.
• The observed depolarization is driven by light-induced changes in MT dipole moments within the membrane.
• MTs hold promise for applications in cardiac electrophysiology (e.g., arrhythmia termination) and neuroscience, enabling cell modulation without genetic intervention.