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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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.

Original languageEnglish (US)
Title of host publicationMultiphoton Microscopy in the Biomedical Sciences XX
EditorsAmmasi Periasamy, Peter T. C. So, Karsten Konig, Karsten Konig
PublisherSPIE
ISBN (Electronic)9781510632516
DOIs
StatePublished - Jan 1 2020
EventMultiphoton Microscopy in the Biomedical Sciences XX 2020 - San Francisco, United States
Duration: Feb 2 2020Feb 4 2020

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume11244
ISSN (Print)1605-7422

Conference

ConferenceMultiphoton Microscopy in the Biomedical Sciences XX 2020
CountryUnited States
CitySan Francisco
Period2/2/202/4/20

Keywords

  • Cardiomyocyte
  • Cardiotoxicity
  • Drug Screening Assay
  • iPSC
  • iPSC-CMs
  • Myosin
  • Second Harmonic Generation
  • SHG

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Atomic and Molecular Physics, and Optics
  • Radiology Nuclear Medicine and imaging

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