Substrate stiffness increases twitch power of neonatal cardiomyocytes in correlation with changes in myofibril structure and intracellular calcium.

Anthony G Rodriguez, Sangyoon J Han, Michael Regnier, Nathan J Sniadecki
Author Information
  1. Anthony G Rodriguez: Department of Bioengineering, University of Washington, Seattle, Washington, USA.

Abstract

During neonatal development, there is an increase in myocardial stiffness that coincides with an increase in the contractility of the heart. In vitro assays have shown that substrate stiffness plays a role in regulating the twitch forces produced by immature cardiomyocytes. However, its effect on twitch power is unclear due to difficulties in measuring the twitch velocity of cardiomyocytes. Here, we introduce what we consider a novel approach to quantify twitch power by combining the temporal resolution of optical line scanning with the subcellular force resolution of micropost arrays. Using this approach, twitch power was found to be greater for cells cultured on stiffer posts, despite having lower twitch velocities. The increased power was attributed in part to improved myofibril structure (increased sarcomere length and Z-band width) and intracellular calcium levels. Immunofluorescent staining of α-actin revealed that cardiomyocytes had greater sarcomere length and Z-band width when cultured on stiffer arrays. Moreover, the concentration of intracellular calcium at rest and its rise with each twitch contraction was greater for cells on the stiffer posts. Altogether, these findings indicate that cardiomyocytes respond to substrate stiffness with biomechanical and biochemical changes that lead to an increase in cardiac contractility.

References

  1. J Physiol. 1995 Feb 15;483 ( Pt 1):131-9 [PMID: 7776227]
  2. Methods Cell Biol. 2007;83:313-28 [PMID: 17613314]
  3. Biophys J. 2008 Oct;95(7):3479-87 [PMID: 18586852]
  4. Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H971-8 [PMID: 14644760]
  5. J Mol Cell Cardiol. 2009 Nov;47(5):603-13 [PMID: 19683533]
  6. Pflugers Arch. 2009 Jun;458(2):337-57 [PMID: 19165498]
  7. Proc R Soc Lond B Biol Sci. 1949 Jun 23;136(883):195-211 [PMID: 18152150]
  8. Science. 2010 Aug 27;329(5995):1078-81 [PMID: 20647425]
  9. Monogr Physiol Soc. 1985;41:1-357 [PMID: 3843415]
  10. Ann N Y Acad Sci. 2010 Feb;1188:121-7 [PMID: 20201894]
  11. J Cell Sci. 2008 Nov 15;121(Pt 22):3794-802 [PMID: 18957515]
  12. Rev Sci Instrum. 2008 Apr;79(4):044302 [PMID: 18447536]
  13. Am J Physiol. 1962 May;202:931-9 [PMID: 13915199]
  14. Circ Res. 1987 Sep;61(3):465-83 [PMID: 2441892]
  15. Biophys J. 2009 Feb;96(3):1189-209 [PMID: 19186154]
  16. Stem Cells. 2008 Aug;26(8):2093-103 [PMID: 18499898]
  17. Biophys J. 2008 Mar 1;94(5):1854-66 [PMID: 17981895]
  18. Nat Phys. 2010 Jun 1;6(6):468-473 [PMID: 20563235]
  19. J Magn Reson Imaging. 2009 Jul;30(1):47-53 [PMID: 19466715]
  20. J Biol Chem. 1985 Mar 25;260(6):3440-50 [PMID: 3838314]
  21. Lab Chip. 2010 Apr 21;10(8):991-8 [PMID: 20358105]
  22. Annu Rev Physiol. 1974;36:187-207 [PMID: 19400661]
  23. J Muscle Res Cell Motil. 1999 Oct;20(7):717-23 [PMID: 10672520]
  24. PLoS Comput Biol. 2009 Nov;5(11):e1000560 [PMID: 19911050]
  25. Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):11954-9 [PMID: 19515816]
  26. Biophys J. 2005 Dec;89(6):L52-4 [PMID: 16214867]
  27. Science. 1966 Sep 30;153(3744):1615-20 [PMID: 5917072]
  28. J Biomech. 2010 Jan 5;43(1):93-8 [PMID: 19819458]
  29. Biochem J. 1977 Dec 15;168(3):599-601 [PMID: 147077]
  30. Circ Res. 1973 Jun;32(6):685-91 [PMID: 4715191]
  31. Physiol Rev. 2000 Apr;80(2):853-924 [PMID: 10747208]
  32. Cardiovasc Res. 2010 Apr 1;86(1):63-71 [PMID: 20019150]
  33. J Physiol. 2007 Jun 1;581(Pt 2):725-39 [PMID: 17347271]
  34. Ann N Y Acad Sci. 2004 May;1015:53-70 [PMID: 15201149]

Grants

  1. HL064387/NHLBI NIH HHS
  2. R01 HL064387/NHLBI NIH HHS
  3. R01 HL065497/NHLBI NIH HHS
  4. HL61683/NHLBI NIH HHS
  5. T32 EB001650/NIBIB NIH HHS
  6. EB001650/NIBIB NIH HHS
  7. R01 HL061683/NHLBI NIH HHS
  8. R24 HL064387/NHLBI NIH HHS
  9. R21 HL097284/NHLBI NIH HHS
  10. HL65497/NHLBI NIH HHS
  11. HL097284/NHLBI NIH HHS

MeSH Term

Animals
Animals, Newborn
Biomechanical Phenomena
Calcium
Intracellular Space
Microscopy, Video
Myocardial Contraction
Myocytes, Cardiac
Myofibrils
Rats
Rats, Inbred F344
Sarcomeres
Time Factors

Chemicals

Calcium

Word Cloud

Created with Highcharts 10.0.0twitchcardiomyocytespowerstiffnessincreasegreaterstifferintracellularcalciumneonatalcontractilitysubstrateapproachresolutionarrayscellsculturedpostsincreasedmyofibrilstructuresarcomerelengthZ-bandwidthchangesdevelopmentmyocardialcoincidesheartvitroassaysshownplaysroleregulatingforcesproducedimmatureHowevereffectunclearduedifficultiesmeasuringvelocityintroduceconsidernovelquantifycombiningtemporalopticallinescanningsubcellularforcemicropostUsingfounddespitelowervelocitiesattributedpartimprovedlevelsImmunofluorescentstainingα-actinrevealedMoreoverconcentrationrestrisecontractionAltogetherfindingsindicaterespondbiomechanicalbiochemicalleadcardiacSubstrateincreasescorrelation

Similar Articles

Cited By