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1 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
2 IonOptix Europe, Wageningen, Netherlands
* To whom correspondence should be addressed. E-mail: gentaro.iribe{at}physiol.ox.ac.uk.
We developed a dynamic force-length (FL) control system for single intact cardiomyocytes that uses a pair of compliant, computer-controlled and piezo translator (PZT)-positioned carbon fibers (CF). CF are attached to opposite cell-ends to afford dynamic and bi-directional control of the cell's mechanical environment. PZT and CF-tip positions, as well as sarcomere length (SL), are simultaneously monitored in real time, and passive/active forces are calculated from CF bending. Cell force and length were dynamically adjusted by corresponding changes in PZT position, to achieve isometric, isotonic, or work-loop style contractions. Functionality of the technique was assessed by studying FL behavior of Guinea pig intact cardiomyocytes. End-diastolic and end-systolic FL relations, obtained with varying pre- and/or afterloads, were near-linear, independent of the mode of contraction, and overlapping for the range of end-diastolic sarcomere lengths tested (1.85-2.05 µm). Instantaneous elastance curves, obtained from FL relation curves, showed an afterload-dependent decrease in time to peak elastance, and slowed relaxation with both increased pre- and afterload. The ability of the present system to independently and dynamically control preload, afterload, and transition between end-diastolic and end-systolic FL coordinates, provides a valuable extension to the range of tools available for the study of single cardiomyocyte mechanics, to foster its interrelation with whole-heart patho-physiology.
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