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Capillary Force Lithography for Cardiac Tissue Engineering
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Traction force microscopy of engineered cardiac tissues.

Francesco Silvio Pasqualini1,2, Ashutosh Agarwal1,2,3,4,5, Blakely Bussie O'Connor1,2

  • 1Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, United States of America.

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Summary

Cardiac tissue stiffness impacts function. Neonate rat ventricular myocytes (NRVM) on soft gels showed poor contractility but high metabolism, indicating inefficient energy use. Healthy stiffness maximized contractile work.

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Area of Science:

  • Biomedical Engineering
  • Cardiovascular Research
  • Mechanobiology

Background:

  • Cardiac tissue development and pathology are sensitive to microenvironmental mechanical factors like extracellular matrix stiffness.
  • Understanding these mechanotransduction pathways is crucial for tissue engineering and disease modeling.

Purpose of the Study:

  • To develop a novel quantitative approach for assessing cardiac structure and function at the tissue level.
  • To investigate the relationship between contractile proficiency and metabolism in neonatal rat ventricular myocytes (NRVM) cultured on substrates of varying stiffness.

Main Methods:

  • Extended classical traction force microscopy to tissue-level preparations.
  • Cultured NRVM on gels mimicking immature (1 kPa), healthy (13 kPa), and diseased (90 kPa) cardiac microenvironments.
  • Quantitatively assessed stress generation, work output, and basal metabolic respiration rate.

Main Results:

  • Tissues on softest gels (1 kPa) produced the least stress and work.
  • NRVM on healthy (13 kPa) and diseased (90 kPa) gels generated significantly higher stresses, with maximal work on healthy gels.
  • Tissues on soft gels showed elevated basal metabolic respiration despite poor contractile performance, suggesting inefficient energy coupling.

Conclusions:

  • Substrate stiffness significantly influences cardiac tissue contractility and metabolism.
  • A novel platform allows quantitative assessment of mechanotransduction in cardiac tissue remodeling.
  • Inefficient energy utilization is observed in NRVM cultured on soft substrates, highlighting the importance of mechanical cues.