Cell shape regulates collagen type I expression in human tendon fibroblasts

Abstract

Understanding the relationship between cell shape and cellular function is important for study of cell biology in general and for regulation of cell phenotype in tissue engineering in particular. In this study, microcontact printing technique was used to create cell-adhesive rectangular and circular islands. The rectangular islands had three aspect ratios: 19.6, 4.9, and 2.2, respectively, whereas circular islands had a diameter of 50 microm. Both rectangular and circular islands had the same area of 1960 microm(2). In culture, we found that human tendon fibroblasts (HTFs) assumed the shapes of these islands. Quantitative immunofluorescence measurement showed that more elongated cells expressed higher collagen type I than did less stretched cells even though cell spreading area was the same. This suggests that HTFs, which assume an elongated shape in vivo, have optimal morphology in terms of expression of collagen type I, which is a major component of normal tendons. Using immunohistochemistry along with cell traction force microscopy (CTFM), we further found that these HTFs with different shapes exhibited variations in actin cytoskeletal structure, spatial arrangement of focal adhesions, and spatial distribution and magnitude of cell traction forces. The changes in the actin cytoskeletal structure, focal adhesion distributions, and traction forces in cells with different shapes may be responsible for altered collagen expression, as they are known to be involved in cellular mechanotransduction.