Three-dimensional microenvironments modulate fibroblast signaling responses

Modes of signaling in fibroblasts can differ substantially depending on whether these cells are in their natural three-dimensional environment compared to artificial two-dimensional culture conditions. Although studying cell behavior in two-dimensional environments has been valuable for understanding biological processes, questions can be raised about their in vivo physiological relevance. This review focuses on some of our research involving fibroblast behavior in cell-derived three-dimensional matrices. Specifically, we examine how these matrices affect cell morphology, adhesion, proliferation, and signaling compared to two-dimensional substrates. We stress the importance of controls for three-dimensional matrix studies and discuss cancer as an example in which altered three-dimensional matrices can influence fibroblast signaling. Studying cells in three-dimensional microenvironments can lead to the design of more physiologically relevant conditions for assaying drug responses and deciphering biological mechanisms.