Hydrogel scaffolds to study cell biology in four dimensions
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troduction Hydrogels represent a robust material system for answering fundamental biological questions relating to three-dimensional cell culture and have been especially effective in investigating the question: How do cells receive and exchange information with their extracellular environment? In living tissues, cells are surrounded by an extracellular matrix (ECM), a network of various protein fibers (e.g., collagen and fibrin) interlaced with glycosaminoglycan chains that provide support and signaling essential for proper development and maintenance of the tissue. The native ECM is actively involved in providing cues that influence cellular processes; for example, adhesion proteins bind to cell-surface receptors that prevent cell death,1 facilitate attachment,2 and influence motility3 in a manner that depends on their concentration and composition (Figure 1).4 In addition, the ECM serves as a reservoir for important growth
factors, often sequestering them in both latent and active forms.5 Rapid proteolytic release and activation of these factors enables localized signaling that is important in promoting wound healing, dictating development, or even furthering cancer progression.5–7 From a general perspective, the ECM is enzymatically degradable to allow for local cellular remodeling.8 These proteinaceous matrices have a high water content and resist mechanical stresses, both of which are properties thought to influence chemical signaling between and within cells through mechanotransduction and diffusion of paracrine, autocrine, and hormone signaling molecules.9 More recent work has focused on de-convoluting the complex roles that mechanical and chemical signals play in dictating cellular development. Diverse tissues in the body have an ECM environment with different compositions and different stiffnesses. For example, the elasticity of various mammalian
Katherine J.R. Lewis, University of Colorado at Boulder; [email protected] Kristi S. Anseth, University of Colorado at Boulder; [email protected] DOI: 10.1557/mrs.2013.54
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MRS BULLETIN • VOLUME 38 • MARCH 2013 • www.mrs.org/bulletin
© 2013 Materials Research Society
HYDROGEL SCAFFOLDS TO STUDY CELL BIOLOGY IN FOUR DIMENSIONS
Figure 1. Schematic of cells within a native extracellular matrix (ECM). Cells (gray) bind specific ECM proteins (green) with cellsurface receptors, such as integrins (brown), to form adhesions important in cell viability, migration, and mechanotransduction. Cell-cell junctions (purple) in addition to cell-ECM adhesions allow the cell to feel mechanical forces in its environment through cytoskeletal stress fibers (red). The ECM is also a reservoir for important soluble cytokines and chemokines (red), which bind to specific cell-surface receptors (orange). The structural fibers of the ECM (yellow) can be cleaved by proteinases secreted by the cells, allowing for localized matrix remodeling. Adapted from Reference 4.
to off-target organs needs to be discovered. For fundamental research, however, animal models have the obv
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