Regulation of cell adhesion and migration by cell-derived matrices

Abstract

Three-dimensional in vitro extracellular matrix models provide a physiological alternative to regular two-dimensional cell culture, though they lack the full diversity of molecular composition and physical properties of whole-animal systems. Cell-derived matrices are extracellular matrices that are the product of matrix secretion and assembly by cells cultured at high density in vitro. After the removal of the cells that produced the matrix, an assembled matrix scaffold is left that closely mimics native stromal fiber organization and molecular content. Cell-derived matrices have been shown to impart in vivo-like responses to cells cultured in these matrices. In this review, we focus on mechanisms through which the distinct molecular and topographical composition of cell-derived matrices directs cellular behavior, specifically through regulation of cell-matrix adhesions and subsequent contributions to the process of cell migration.

Keywords: 3D cell migration; Cell-derived matrix (CDM); Extracellular matrix; Fibrillar topography; Matrix adhesions; Matrix elasticity.

Figure 1. Fibroblast migration in 3D cell-derived matrix

Left: Maximum projection confocal image of a human foreskin fibroblast (HFF) embedded within a matrix containing oriented CDM fibronectin fibrils (magenta, anti-fibronectin immunostaining). Cytoskeletal architecture visualized by staining for actin (blue, phalloidin) and paxillin-containing focal adhesions (yellow, anti-paxillin). Right: Maximum projection image of focal adhesion profile of paxillin-containing adhesions during migration in CDM.