Computational study of voltage sensitive dyes in polarized membranes

SOSA, MICAELA; GALASSI, VANESA; DEL PÓPOLO, MARIO; BERTONI, ANDRÉS; SÁNCHEZ, CRISTIÁN

Buenos Aires

Simposio; I Simposio de Modelado para Biociencias y Nanomateriales en Argentina (SiModAr); 2022

UNSAM - UBA

Voltage Sensitive Dyes (VSD) are optically active molecules with the ability to report changes in the membrane potential via changes in their own spectral properties, such as shifts in the wavelength of maximum absorption or emission, or changes of absorption or fluorescence intensity at a selected wavelength. VSDs are used in optical imaging of transmembrane potentials, as they offer higher spatio-temporal resolution  than standard electrophysiological methods. However, the application of optical imaging has significant challenges associated with the biophysical constraints imposed by the experimental measurements, difficulties that could be ameliorated with a better understanding of the voltage sensing mechanisms.We address the question of whether the spectral response of Indocyanine Green, a case example VSD, is due to electrochromism resulting from the direct interaction of the dye with the transmembrane electric field, or to changes in the dye/membrane configuration.The research focuses on developing a computational protocol that allows to evaluate the molecular basis underlying the voltage sensitivity of the optical response. We first use molecular dynamics simulations to assess the energetics and characterize configurations of the dye partitioned into polarized lipid membranes. Secondly, we use electron dynamics calculations to obtain the absorption spectra of the fluorescent molecule. Finally, we compare results obtained from different polarized states, and describe the biophysical mechanism underlying the optical response of the VSD. Our aim, in the long term, is to enhance the optical differential response of VSDs by rational design of molecular derivatives from currently available VSDs.