Imperial College London
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DrPeterWright

Faculty of Medicine, National Heart & Lung Institute

Honorary Research Fellow
 
 
 
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Contact

 

peter.wright09

 
 
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Location

 

L-Block 424ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wright:2020:10.3389/fphys.2020.00612,
author = {Wright, P and Tsui, S and Francis, A and MacLeod, K and Marston, S},
doi = {10.3389/fphys.2020.00612},
journal = {Frontiers in Physiology},
title = {Approaches to high-throughput analysis of cardiomyocyte contractility},
url = {http://dx.doi.org/10.3389/fphys.2020.00612},
volume = {11},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The measurement  of  the  contractile  behavior  of  single  cardiomyocytes has made  a  significant contribution  to  our  understanding  of  the  physiologyand  pathophysiology of  the  myocardium. However,   the isolation   of cardiomyocytes introducesvarious technical   and   statistical issues. Traditional video and  fluorescence microscopy  techniques  based  around  conventional  microscopy systems result in low throughput experimental studies, in which single cells are studied over the course of a pharmacologicalor physiologicalintervention. We describe a new approach to these experiments made possible with a new piece of instrumentation, the CytoCypher High-Throughput System (CC-19HTS).Wecan assess the shortening of sarcomeres, cell length, Ca2+handling and cellular morphology of almost 4 cells perminute. Thisincrease in productivity means that batch-to-batch variation can be identified as a major source of variability. The speed of acquisition means that sufficientnumbers of cells in  each  preparation can  be  assessed  for  multiple  conditions reducingthese batch  effects.  We demonstrate the different temporal scales over which the CC-HTS can acquire data. We use statistical analysis methods thatcompensate for the hierarchical effects of clustering withinheart preparations anddemonstrate asignificant false positive rate which is potentially present in conventional studies.  We  demonstrate  a  more  stringent  way  toperform  these  tests. The  baseline  morphological  and functional  characteristics  of  rat,  mouse,  guinea  pig  and  human  cells  are  explored. Finally,  we  show data from concentration response experiments revealing the usefulnessof the CC-HTSin suchstudies. We specifically focus on the effects of agents thatdirectly or indirectly affect the activity of the motor proteins involved in the production of cardiomyocyte contraction. A variety of myocardial preparations with differing levels of complexity are in use (e.g. isolated muscl
AU  - Wright,P
AU  - Tsui,S
AU  - Francis,A
AU  - MacLeod,K
AU  - Marston,S
DO  - 10.3389/fphys.2020.00612
PY  - 2020///
SN  - 1664-042X
TI  - Approaches to high-throughput analysis of cardiomyocyte contractility
T2  - Frontiers in Physiology
UR  - http://dx.doi.org/10.3389/fphys.2020.00612
UR  - http://hdl.handle.net/10044/1/80510
VL  - 11
ER  -
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