Monitoring drug induced changes in cardiomyocyte contractility with second harmonic generation (SHG) microscopy

Che-Wei Chang; Hillary K. J. Kao; Yao-Hui Sun; Dalyir I. Pretto; Deborah K. Lieu; James W. Chan

doi:10.1117/12.2546825

14 February 2020 Monitoring drug induced changes in cardiomyocyte contractility with second harmonic generation (SHG) microscopy

Che-Wei Chang, Hillary K. J. Kao, Yao-Hui Sun, Dalyir I. Pretto, Deborah K. Lieu, James W. Chan

Author Affiliations +

Proceedings Volume 11244, Multiphoton Microscopy in the Biomedical Sciences XX; 112442H (2020) https://doi.org/10.1117/12.2546825
Event: SPIE BiOS, 2020, San Francisco, California, United States

Abstract

The cost of taking a drug to market can exceed $2 billion dollars. The escalating cost of drug discovery is a major motivating factor for seeking new methods to predict the safety and efficacy of new compounds as early as possible in the drug development process to avoid drug attrition during late phases of clinical trials or even the withdrawal of approved drugs. Cardiotoxicity accounts for nearly 30% of US post-marketing drug withdrawal and remains a major concern to the point where the US Food and Drug Administration (FDA) is focused on in vitro cardiotoxicity screening to minimize cardiac risks associated with drugs. A technique that can directly quantify interactions between drugs and cardiomyocytes without the interference from exogenous genetic or chemical labels would be highly beneficial for directly screening these new drugs. Our group has previously shown that second harmonic generation (SHG) signals generated from myosin filaments in cardiomyocytes can be used as a robust label-free optical technique for recording cell shortening dynamics at high spatial and temporal resolution due to the ability of the myosin rod domains in heart muscle cells to emit the frequency-doubled light. The dynamics is recorded without adding any fluorescent labels that may otherwise affect and modify the natural cell contractility of the cell. In this study, we investigated the use of SHG microscopy for measuring drug-induced changes in cardiac cell contractility and discuss its feasibility as a tool for screening drugs and evaluating cardiotoxicity.

Citation Download Citation

Che-Wei Chang, Hillary K. J. Kao, Yao-Hui Sun, Dalyir I. Pretto, Deborah K. Lieu, and James W. Chan "Monitoring drug induced changes in cardiomyocyte contractility with second harmonic generation (SHG) microscopy", Proc. SPIE 11244, Multiphoton Microscopy in the Biomedical Sciences XX, 112442H (14 February 2020); https://doi.org/10.1117/12.2546825

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KEYWORDS

Second-harmonic generation

Microscopes

Microscopy

Harmonic generation

Stem cells

Heart

In vitro testing

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