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

Valentina Sesti; Arianna Magni; Matteo Moschetta; Chiara Florindi; Marlene E. Pfeffer; Mattia Lorenzo DiFrancesco; Michele Guizzardi; Giulia Folpini; Luca Sala; Alessandra Gilda Ritacca; Beatrice Campanelli; Paola Moretti; Giuseppe Maria Paternò; Luca Maragliano; Matteo Tommasini; Francesco Lodola; Elisabetta Colombo; Fabio Benfenati; Chiara Bertarelli; Guglielmo Lanzani

doi:10.1038/s41377-024-01669-x

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

Original Articles

- Membrane-targeted push-pull azobenzenes for the optical modulation of membrane potential
- Light: Science & Applications Vol. 14, Issue 1, Pages: 93-109(2025)
- Affiliations：
  
  1.Department of Chemistry, Materials and Chemical Engineering, "Giulio Natta" Politecnico di Milano, Milano 20133, Italy
  2.Center for Nanoscience and Technology, Istituto Italiano di Tecnologia, Milano 20134, Italy
  3.Department of Physics, Politecnico di Milano, Milano 20133, Italy
  4.Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano 20126, Italy
  5.Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genova 16132, Italy
  6.IRCCS Ospedale Policlinico San Martino, Genova 16132, Italy
  7.Institute for Photonics and Nanotechnologies (IFN), National Research Council (CNR), Milano 20133, Italy
  8.Istituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milano 20095, Italy
  9.Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona 60131, Italy
  10.Present address: Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA
- Author bio：
  
  Chiara Bertarelli (chiara.bertarelli@polimi.it)
  Guglielmo Lanzani (guglielmo.lanzani@iit.it)
- Funds：
- DOI：10.1038/s41377-024-01669-x
  CLC：
- Published：31 January 2025，
  
  Published Online：01 January 2025，
  
  Received：09 April 2024，
  
  Revised：08 October 2024，
  
  Accepted：2024-10-24
- Accepted：
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Sesti, V. et al. Membrane-targeted push-pull azobenzenes for the optical modulation of membrane potential. Light: Science & Applications, 14, 93-109 (2025).
DOI：

Sesti, V. et al. Membrane-targeted push-pull azobenzenes for the optical modulation of membrane potential. Light: Science & Applications, 14, 93-109 (2025). DOI： 10.1038/s41377-024-01669-x.

摘要

Abstract

We introduce a family of membrane-targeted azobenzenes (MTs) with a push-pull character as a new tool for cell stimulation. These molecules are water soluble and spontaneously partition in the cell membrane. Upon light irradiation

they isomerize from

trans

cis

changing the local charge distribution and thus stimulating the cell response. Specifically

MTs photoisomerization induces clear and reproducible depolariz

ation. The most promising species

MTP2

was extensively studied. Time-resolved spectroscopy techniques provide insights into the excited state evolution and a complete understanding of its isomerization reaction. Molecular Dynamics simulations reveal the spontaneous and stable partitioning of the compound into the cellular membrane

without significant alterations to the bilayer thickness. MTP2 was tested in different cell types

including HEK293T cells

primary neurons

and cardiomyocytes

and a steady depolarization is always recorded. The observed membrane potential modulation in in-vitro models is attributed to the variation in membrane surface charge

resulting from the light-driven modulation of the MT dipole moment within the cell membrane. Additionally

a developed mathematical model successfully captures the temporal evolution of the membrane potential upon photostimulation. Despite being insufficient for triggering action potentials

the rapid light-induced depolarization holds potential applications

particularly in cardiac electrophysiology. Low-intensity optical stimulation with these modulators could influence cardiac electrical activity

demonstrating potential efficacy in destabilizing and terminating cardiac arrhythmias. We anticipate the MTs approach to find applications in neuroscience

biomedicine

and biophotonics

providing a tool for modulating cell physiology without genetic interventions.

关键词

Keywords

references

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