title: Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering and Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Deok-Ho
authors.initials: DH
authors.lastname: Kim
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Lipke
authors.forename: Pilnam
authors.initials: P
authors.lastname: Kim
authors.forename: Raymond
authors.initials: R
authors.lastname: Cheong
authors.forename: Susan
authors.initials: S
authors.lastname: Thompson
authors.forename: Michael
authors.initials: M
authors.lastname: Delannoy
authors.forename: Kahp-Yang
authors.initials: KY
authors.lastname: Suh
authors.forename: Leslie
authors.initials: L
authors.lastname: Tung
authors.forename: Andre
authors.initials: A
authors.lastname: Levchenko
mesh_terms: 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
chemical_list: D020100:Hydrogels; D011092:Polyethylene Glycols