Premium
Hepatocellular phenotype in Vitro is influenced by biophysical features of the collagenous substratum
Author(s) -
Lindblad William J.,
Schuetz Erin G.,
Redford Kaye S.,
Guzelian Philip S.
Publication year - 1991
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840130213
Subject(s) - matrigel , extracellular matrix , basement membrane , microbiology and biotechnology , in vitro , biology , messenger rna , type i collagen , hepatocyte , extracellular , cytoskeleton , rna , biochemistry , biophysics , chemistry , cell , endocrinology , gene
Hepatocytes maintained on different substrata in vitro possess strikingly different morphological and biochemical features. Rounded, multicellular aggregates of hepatocytes are seen if the cells are plated onto Matrigel, a reconstituted basement membrane, whereas a flattened, monolayer of hepatocytes is observed with Vitrogen. Hepatocellular protein synthesis is much greater on the Matrigel, although collagen biosynthesis appears selectively enhanced on Vitrogen‐grown hepatocytes. We determined that denatured type I collagen could be substituted for Matrigel as the substratum, with the hepatocytes remaining the same both morphologically and biochemically. This suggested that the cells respond to the biophysical state of the extracellular matrix not only to protein sequences that determine a binding site. Measurement of steady‐state messenger RNA levels within cells cultured onto different matrices indicated that the fluid substrata of either Matrigel or denatured type I collagen were facilitative for induction of cytochrome P‐450b/e, which was not seen with the rigid type I collagen substrata. In contrast the messenger RNA level for the cytoskeletal protein actin was decreased on the fluid matrices, suggesting that the rounded cells had a lower requirement for this protein. These findings indicate that hepatocytes are responsive to the biophysical state of the extracellular matrix, which can lead to significant changes in gene expression by the cells. (H EPATOLOGY 1991;13:282–288).