Computational study of voltage sensitive dyes in polarized membranes

SOSA, MICAELA; ANDRES BERTONI; SANCHEZ, CRISTIÁN; MARIO G DEL POPOLO; VANESA GALASSI

Rosario

Congreso; L Reunión Anual de la Sociedad Argentina de Biofísica; 2022

Universidad Nacional de Rosario IBR-CONICET

Voltage Sensitive Dyes (VSD) are optically active molecules with the ability to reportchanges in the membrane potential via changes in their own spectral properties, such asshifts in the wavelength of maximum absorption or emission, or changes of absorption orfluorescence intensity at a selected wavelength. VSDs are used in optical imaging oftransmembrane potentials, as they offer higher spatio-temporal resolution than standardelectrophysiological methods. However, the application of optical imaging has significantchallenges associated with the biophysical constraints imposed by the experimentalmeasurements, difficulties that could be ameliorated with a better understanding of thevoltage sensing mechanisms.We address the question of whether the spectral response of Indocyanine Green, a caseexample VSD, is due to electrochromism resulting from the direct interaction of the dyewith the transmembrane electric field, or to changes in the dye/membrane configuration.The research focuses on developing a computational protocol that allows to evaluate themolecular basis underlying the voltage sensitivity of the optical response. We first usemoleculardynamics simulations to assess the energetics and characterize configurations of the dyepartitioned into polarized lipid membranes. Secondly, we use electron dynamicscalculations to obtain the absorption spectra of the fluorescent molecule. Finally, wecompare results obtained from different polarized states, and describe the biophysicalmechanism underlying the optical response of the VSD. Our aim, in the long term, is toenhance the optical differential response of VSDs by rational design of molecularderivatives from currently available VSDs.AcknowldegmentsWe want to acknowledge CONICET and ANPCyT for the funding.