Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs.
Heart tissue possesses complex structural organization on multiple scales, from macro- to nano-, but nanoscale control of cardiac function has not been extensively analyzed. Inspired by ultrastructural analysis of the native tissue, we constructed a scalable, nanotopographically controlled model of myocardium mimicking the in vivo ventricular organization. Guided by nanoscale mechanical cues provided by the underlying hydrogel, the tissue constructs displayed anisotropic action potential propagation and contractility characteristic of the native tissue. Surprisingly, cell geometry, action potential conduction velocity, and the expression of a cell-cell coupling protein were exquisitely sensitive to differences in the substratum nanoscale features of the surrounding extracellular matrix. We propose that controlling cell-material interactions on the nanoscale can stipulate structure and function on the tissue level and yield novel insights into in vivo tissue physiology, while providing materials for tissue repair.
Kim
Deok-Ho
DH
Department of Biomedical Engineering and Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Lipke
Elizabeth A
EA
Kim
Pilnam
P
Cheong
Raymond
R
Thompson
Susan
S
Delannoy
Michael
M
Suh
Kahp-Yang
KY
Tung
Leslie
L
Levchenko
Andre
A
D000818:Animals; D005109:Extracellular Matrix / Q000648:ultrastructure; D006321:Heart / Q000033:anatomy & histology*; D006801:Humans; D020100:Hydrogels; D008855:Microscopy, Electron, Scanning / Q000379:methods; D009206:Myocardium / Q000648:ultrastructure*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D011092:Polyethylene Glycols; D051381:Rats; D023822:Tissue Engineering / Q000379:methods
D020100:Hydrogels; D011092:Polyethylene Glycols