Opto-SICM framework combines optogenetics with scanning ion conductance microscopy for probing cell-to-cell contacts

We present a novel framework, Opto-SICM, for studies of cellular interactions in live cells with high spatiotemporal resolution. The approach combines scanning ion conductance microscopy, SICM, and cell-type-specific optogenetic interrogation. Light-excitable cardiac fibroblasts (FB) and myofibrobla...

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Bibliographic Details
Published in:Communications biology 2023-11, Vol.6 (1), p.1131-1131, Article 1131
Main Authors: Song, Qianqian, Alvarez-Laviada, Anita, Schrup, Sarah E., Reilly-O’Donnell, Benedict, Entcheva, Emilia, Gorelik, Julia
Format: Article
Language:English
Subjects:
14/3
14/33
631/1647/2253
692/4019/592/75/230
Biology
Biomedical and Life Sciences
Cardiomyocytes
Cell migration
Conductance
Connexin 43
Coronary artery disease
Fibroblasts
Gap junctions
Genetics
Heart diseases
Information processing
Life Sciences
Light microscopy
Microscopy
Myocytes, Cardiac
Myofibroblasts
Optics
Optogenetics
Scanning
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Summary:We present a novel framework, Opto-SICM, for studies of cellular interactions in live cells with high spatiotemporal resolution. The approach combines scanning ion conductance microscopy, SICM, and cell-type-specific optogenetic interrogation. Light-excitable cardiac fibroblasts (FB) and myofibroblasts (myoFB) were plated together with non-modified cardiomyocytes (CM) and then paced with periodic illumination. Opto-SICM reveals the extent of FB/myoFB-CM cell-cell contacts and the dynamic changes over time not visible by optical microscopy. FB-CM pairs have lower gap junctional expression of connexin-43 and higher contact dynamism compared to myoFB-CM pairs. The responsiveness of CM to pacing via FB/myoFB depends on the dynamics of the contact but not on the area. The non-responding pairs have higher net cell-cell movement at the contact. These findings are relevant to cardiac disease states, where adverse remodeling leads to abnormal electrical excitation of CM. The Opto-SICM framework can be deployed to offer new insights on cellular and subcellular interactions in various cell types, in real-time. Opto-SCIM combines scanning ion conductance microscopy with optogenetic interrogation to study the hetero-cellular interactions between cardiac fibroblasts or myofibroblasts and cardiomyocytes.
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-023-05509-3