Multimodal on-axis platform for all-optical electrophysiology with near-infrared probes in human stem-cell-derived cardiomyocytes

Aleksandra Klimas; Gloria Ortiz; Steven C Boggess; Evan W Miller; Emilia Entcheva

doi:10.1016/j.pbiomolbio.2019.02.004

Multimodal on-axis platform for all-optical electrophysiology with near-infrared probes in human stem-cell-derived cardiomyocytes

Prog Biophys Mol Biol. 2020 Aug:154:62-70. doi: 10.1016/j.pbiomolbio.2019.02.004. Epub 2019 Mar 5.

Authors

Aleksandra Klimas¹, Gloria Ortiz², Steven C Boggess², Evan W Miller³, Emilia Entcheva⁴

Affiliations

¹ Department of Biomedical Engineering, The George Washington University, Washington, DC, 20052, USA.
² Department of Chemistry, University of California, Berkeley, CA, 94720, USA.
³ Department of Chemistry, University of California, Berkeley, CA, 94720, USA; Department Molecular & Cell Biology, University of California, Berkeley, CA, 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, CA, 94720, USA.
⁴ Department of Biomedical Engineering, The George Washington University, Washington, DC, 20052, USA. Electronic address: entcheva@gwu.edu.

Abstract

Combined optogenetic stimulation and optical imaging permit scalable, contact-free high-throughput probing of cellular electrophysiology and optimization of stem-cell derived excitable cells, such as neurons and muscle cells. We report a new "on-axis" configuration (combined single optical path for stimulation and for multiparameter imaging) of OptoDyCE, our all-optical platform for studying human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) and other cell types, optically driven by Channelrhodopsin2 (ChR2). This solid-state system integrates optogenetic stimulation with temporally-multiplexed simultaneous recording of membrane voltage (V_m) and intracellular calcium ([Ca²⁺]_i) dynamics using a single photodetector. We demonstrate the capacity for combining multiple spectrally-compatible actuators and sensors, including newer high-performance near-infrared (NIR) voltage probes BeRST1 and Di-4-ANBDQBS, to record complex spatiotemporal responses of hiPSC-CMs to drugs in a high-throughput manner.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Calcium / metabolism
Electrophysiology / instrumentation*
Humans
Induced Pluripotent Stem Cells / cytology*
Infrared Rays*
Intracellular Space / metabolism
Myocytes, Cardiac / cytology*
Myocytes, Cardiac / metabolism
Optical Phenomena*

Substances

Calcium

Abstract

Publication types

MeSH terms

Substances

Grants and funding