Modulation of cardiac myocyte phenotype in vitro by the composition and orientation of the extracellular matrix

D. G. Simpson, Louis Terracio, M. Terracio, R. L. Price, D. C. Turner, T. K. Borg

Research output: Contribution to journalArticle

Abstract

Cellular phenotype is the result of a dynamic interaction between a cell's intrinsic genetic program and the morphogenetic signals that serve to modulate the extent to which that program is expressed. In the present study we have examined how morphogenetic information might be stored in the extracellular matrix (ECM) and communicated to the neonatal heart cell (NHC) by the cardiac α1β1 integrin molecule. A thin film of type I collagen (T1C) was prepared with a defined orientation. This was achieved by applying T1C to the peripheral edge of a 100 mm culture dish. The T1C was then drawn across the surface of the dish in a continuous stroke with a sterile cell scraper and allowed to polymerize. When NHCs were cultured on this substrate, they spread, as a population, along a common axis in parallel with the gel lattice and expressed an in vivo-like phenotype. individuat NHCs displayed an elongated, rod-like shape and disclosed parallel arrays of myofibrils. These phenotypic characteristics were maintained for at least 4 weeks in primary culture. The evolution of this tissue-like organizational pattern was dependant upon specific interactions between the NHCs and the collagen-based matrix that were mediated by the cardiac α1β1 integrin complex. This conclusion was supported by a variety of experimental results. Altering the tertiary structure of the matrix or blocking the extracellular domains of either the cardiac α1 or β1 integrin chain inhibited the expression of the tissue-like pattern of organization. Neither cell-to-cell contact or contractile function were necessary to induce the formation of the rod-like cell shape. However, beating activity was necessary for the assembly of a well-differentiated myofibrillar apparatus. These data suggest that the cardiac α1β1 integrin complex serves to detect and transduce phenotypic information stored within the tertiary structure of the surrounding matrix.

Original languageEnglish (US)
Pages (from-to)89-105
Number of pages17
JournalJournal of Cellular Physiology
Volume161
Issue number1
DOIs
StatePublished - Oct 1994

Fingerprint

Cardiac Myocytes
Integrins
Extracellular Matrix
Modulation
Phenotype
Chemical analysis
Tissue
Collagen Type I
Cell Shape
Myofibrils
Collagen
Gels
Cells
Thin films
Molecules
Stroke
In Vitro Techniques
Substrates
Population

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Modulation of cardiac myocyte phenotype in vitro by the composition and orientation of the extracellular matrix. / Simpson, D. G.; Terracio, Louis; Terracio, M.; Price, R. L.; Turner, D. C.; Borg, T. K.

In: Journal of Cellular Physiology, Vol. 161, No. 1, 10.1994, p. 89-105.

Research output: Contribution to journalArticle

Simpson, D. G. ; Terracio, Louis ; Terracio, M. ; Price, R. L. ; Turner, D. C. ; Borg, T. K. / Modulation of cardiac myocyte phenotype in vitro by the composition and orientation of the extracellular matrix. In: Journal of Cellular Physiology. 1994 ; Vol. 161, No. 1. pp. 89-105.
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