Optogenetic and sonogenetic pacing of unmodified cardiac tissue upon quick integration with specialized biological actuators
- 1The George Washington University
Abstract
Electrical stimulation for cardiac pacing has been in clinical use for 100 years and it is the current standard. Alternative scalable pacing methods that are contactless, with good spatial precision and can also be cell-selective are of interest for both in vitro and in vivo applications. Cardiac pacing by light or by ultrasound (US) can be achieved using optogenetic transduction of the tissue and by enhancing responsiveness to ultrasound. In this work we create specialized biological actuators (cell spheroids) out of generic human cells, modified optogenetically (using Channelrhodopsin2) and sonogenetically (using human Piezo1), guide them to a desired location to promote quick integration with unmodified cardiac syncytia within less than two hours. We quantify their ability to confer pacing by light or US and to entrain the native cardiac tissue, modeled here with human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) grown in monolayers, quasi-3D oriented microtissues or cell spheroids. Magnetic guidance (via magnetic nanoparticles) speeds up integration and facilitates positioning to optimize electrotonic load for pacing; size match and three-dimensional growth also accelerate integration. Computational modeling corroborates the possibility to pace by light and by US. Using optogenetically-gated US pulses (0.5 MHz), we show entrainment in voltage and calcium responses and identify the best performing configurations. Experiments reveal the potential role of Piezo1, esp. when activated with Yoda1. The approach is shown to work with physiologically relevant heart cells, such as human cardiac fibroblasts as optimized actuators, and therefore can be considered for in vivo applications as part of heart regeneration efforts. High-throughput cardiotoxicity testing and drug screening in vitro can directly benefit from deployment of such biological actuators.
Related
- Quantifying c-di-GMP: A Call for Integration of Biological and Chemical Approaches
- Multiscale harmonization, semantic integration, and immersive exploration of single-cell data in support of novel biological insights
- Biopesticides and biological control agents: advances, integration, and prospects for sustainable pest management
- iPSC-Derived Chondroprogenitors as a Promising Cell Source for Cartilage Engineering: A Comparison with MSCs in Unmodified and Peptide-Functionalized Alginate Hydrogels
- Optogenetic modeling of wake-like transcriptional progression in human SH-SY5Y neuronal cells
BibTeX
@misc{pettebone2026optogenetic,
title = {{Optogenetic and sonogenetic pacing of unmodified cardiac tissue upon quick integration with specialized biological actuators}},
author = {M. E. Pettebone and J. L. Han and A. Forouzandehmehr and O. Chesla and C. J. Chua and M. R. Pozo and Y. W. Heinson and W. Liu and E. Entcheva},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.760310},
url = {https://www.biorxiv.org/content/10.64898/2026.10.19.760310v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Optogenetic and sonogenetic pacing of unmodified cardiac tissue upon quick integration with specialized biological actuators
AU - M. E. Pettebone
AU - J. L. Han
AU - A. Forouzandehmehr
AU - O. Chesla
AU - C. J. Chua
AU - M. R. Pozo
AU - Y. W. Heinson
AU - W. Liu
AU - E. Entcheva
PY - 2026
DA - 2026/10/19
PB - bioRxiv
DO - 10.64898/2026.10.19.760310
UR - https://www.biorxiv.org/content/10.64898/2026.10.19.760310v1
AB - Electrical stimulation for cardiac pacing has been in clinical use for 100 years and it is the current standard. Alternative scalable pacing methods that are contactless, with good spatial precision and can also be cell-selective are of interest for both in vitro and in vivo applications. Cardiac pacing by light or by ultrasound (US) can be achieved using optogenetic transduction of the tissue and by enhancing responsiveness to ultrasound. In this work we create specialized biological actuators (cell spheroids) out of generic human cells, modified optogenetically (using Channelrhodopsin2) and sonogenetically (using human Piezo1), guide them to a desired location to promote quick integration with unmodified cardiac syncytia within less than two hours. We quantify their ability to confer pacing by light or US and to entrain the native cardiac tissue, modeled here with human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) grown in monolayers, quasi-3D oriented microtissues or cell spheroids. Magnetic guidance (via magnetic nanoparticles) speeds up integration and facilitates positioning to optimize electrotonic load for pacing; size match and three-dimensional growth also accelerate integration. Computational modeling corroborates the possibility to pace by light and by US. Using optogenetically-gated US pulses (0.5 MHz), we show entrainment in voltage and calcium responses and identify the best performing configurations. Experiments reveal the potential role of Piezo1, esp. when activated with Yoda1. The approach is shown to work with physiologically relevant heart cells, such as human cardiac fibroblasts as optimized actuators, and therefore can be considered for in vivo applications as part of heart regeneration efforts. High-throughput cardiotoxicity testing and drug screening in vitro can directly benefit from deployment of such biological actuators.
ER -