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Anisotropic stretch‐induced hypertrophy in neonatal ventricular myocytes micropatterned on deformable elastomers
Author(s) -
Gopalan Sindhu M.,
Flaim Chris,
Bhatia Sangeeta N.,
Hoshijima Masahiko,
Knoell Ralph,
Chien Kenneth R.,
Omens Jeffrey H.,
McCulloch Andrew D.
Publication year - 2002
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.10506
Subject(s) - sarcomere , biophysics , myocyte , materials science , c2c12 , phalloidin , cytoskeleton , extracellular matrix , myofibril , actin , chemistry , anatomy , cell , microbiology and biotechnology , biology , myogenesis , biochemistry
Because cell shape and alignment, cell–matrix adhesion, and cell–cell contact can all affect growth, and because mechanical strains in vivo are multiaxial and anisotropic, we developed an in vitro system for engineering aligned, rod‐shaped, neonatal cardiac myocyte cultures. Photolithographic and microfluidic techniques were used to micropattern extracellular matrices in parallel lines on deformable silicone elastomers. Confluent, elongated, aligned myocytes were produced by varying the micropattern line width and collagen density. An elliptical cell stretcher applied 2:1 anisotropic strain statically to the elastic substrate, with the axis of greatest stretch (10%) either parallel or transverse to the myofibrils. After 24 h, the principal strain parallel to myocytes did not significantly alter myofibril accumulation or expression of atrial natriuretic factor (ANF), connexin‐43 (Cx‐43), or N ‐cadherin (by indirect immunofluorescent antibody labeling and immunoblotting) compared with unstretched controls. In contrast, 10% transverse principal strain resulted in continuous staining of actin filaments (rhodamine phalloidin); increased immunofluorescent labeling of ANF, Cx‐43, and N ‐cadherin; and upregulation of protein signal intensity by western blotting. By using microfabrication and microfluidics to control cell shape and alignment on an elastic substrate, we found greater effects for transverse than for longitudinal stretch in regulating sarcomere organization, hypertrophy, and cell‐to‐cell junctions. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 578–587, 2003.