Nanoscale Cues Regulate the Structure and Function of Macroscopic Cardiac Tissue Constructs

Kim DH, Lipke EA, Kim P, Cheong R, Thompson S, Delannoy M, Suh KY (1), Tung L (2), Levchenko A (2)

(1) Seoul National University, (2) Johns Hopkins University

Proc Natl Acad Sci U S A, 107(2):565-70(2010)

Link To Paper

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.

Keywords: Action potential, Cardiomyocytes, Extracellular matrix, Nanotopography, Tissue engineering

Materials & Methods: Nanopatterned substrata of PEG hydrogels were fabricated by using UV-assisted capillary lithography-based nanomolding techniques as previously described (20). NRVMs were isolated as previously described (13) and then cultured on the nanopatterned PEG substratum to form the confluent monolayer. Optical mapping, contraction mapping, Western blot, SEM/TEM analysis, and immunostaining experiments were performed 6–7 days after plating. Quantitative analysis of conduction velocity and contraction was performed by using custom-written MATLAB scripts. Details are described in the SI Text.

Microscopic Technique: Scanning electron microscopy, Transmission electron microscopy

Cell Type(s): Muscle Cells, Neonatal Rat Ventricular Myocytes (NRVMs)