Optical modulation of excitation-contraction coupling in human-induced pluripotent stem cell-derived cardiomyocytes
Vito Vurro,
Beatrice Federici,
Carlotta Ronchi,
Chiara Florindi,
Valentina Sesti,
Silvia Crasto,
Claudia Maniezzi,
Camilla Galli,
Maria Rosa Antognazza,
Chiara Bertarelli,
Elisa Di Pasquale,
Guglielmo Lanzani,
Francesco Lodola
Affiliations
Vito Vurro
Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia, Via Raffaele Rubattino, 81, 20134 Milan, Italy
Beatrice Federici
Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia, Via Raffaele Rubattino, 81, 20134 Milan, Italy
Carlotta Ronchi
Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia, Via Raffaele Rubattino, 81, 20134 Milan, Italy
Chiara Florindi
Department of Biotechnology and Biosciences, University of Milan-Bicocca, Building U3 - BIOS, Piazza della Scienza, 2, 20126 Milan, Italy
Valentina Sesti
Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia, Via Raffaele Rubattino, 81, 20134 Milan, Italy; Department of Chemistry, Materials and Engineering Chemistry ‘Giulio Natta’, Politecnico di Milano, Piazza Leonardo da Vinci, 32, 20133 Milan, Italy
Silvia Crasto
Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy, 20138 Milan, Italy; IRCCS-Humanitas Research Hospital, 20089 Rozzano, Italy
Claudia Maniezzi
Department of Biotechnology and Biosciences, University of Milan-Bicocca, Building U3 - BIOS, Piazza della Scienza, 2, 20126 Milan, Italy
Camilla Galli
IRCCS-Humanitas Research Hospital, 20089 Rozzano, Italy
Maria Rosa Antognazza
Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia, Via Raffaele Rubattino, 81, 20134 Milan, Italy
Chiara Bertarelli
Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia, Via Raffaele Rubattino, 81, 20134 Milan, Italy; Department of Chemistry, Materials and Engineering Chemistry ‘Giulio Natta’, Politecnico di Milano, Piazza Leonardo da Vinci, 32, 20133 Milan, Italy
Elisa Di Pasquale
Institute of Genetic and Biomedical Research (IRGB), UOS of Milan, National Research Council of Italy, 20138 Milan, Italy; IRCCS-Humanitas Research Hospital, 20089 Rozzano, Italy
Guglielmo Lanzani
Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia, Via Raffaele Rubattino, 81, 20134 Milan, Italy; Department of Physics, Politecnico di Milano, Piazza Leonardo da Vinci, 32, 20133 Milan, Italy; Corresponding author
Francesco Lodola
Center for Nano Science and Technology @PoliMi, Istituto Italiano di Tecnologia, Via Raffaele Rubattino, 81, 20134 Milan, Italy; Department of Biotechnology and Biosciences, University of Milan-Bicocca, Building U3 - BIOS, Piazza della Scienza, 2, 20126 Milan, Italy; Corresponding author
Summary: Non-genetic photostimulation is a novel and rapidly growing multidisciplinary field that aims to induce light-sensitivity in living systems by exploiting exogeneous phototransducers. Here, we propose an intramembrane photoswitch, based on an azobenzene derivative (Ziapin2), for optical pacing of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The light-mediated stimulation process has been studied by applying several techniques to detect the effect on the cell properties. In particular, we recorded changes in membrane capacitance, in membrane potential (Vm), and modulation of intracellular Ca2+ dynamics. Finally, cell contractility was analyzed using a custom MATLAB algorithm. Photostimulation of intramembrane Ziapin2 causes a transient Vm hyperpolarization followed by a delayed depolarization and action potential firing. The observed initial electrical modulation nicely correlates with changes in Ca2+ dynamics and contraction rate. This work represents the proof of principle that Ziapin2 can modulate electrical activity and contractility in hiPSC-CMs, opening up a future development in cardiac physiology.
