Dynamic Substrates for Cell Biology
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Dynamic Substrates for Cell Biology Milan Mrksich Abstract The development of dynamic substrates that can modulate the behavior of adherent cells is important for fundamental studies in cell biology, applications in biomaterials, and engineering microsystems that combine cellular and material components. This review outlines several strategies based on physical transduction schemes (including electrical, photochemical, thermal, and mechanical forces) for designing interfaces that are active and can signal changes in the behavior of attached cells. Keywords: biointerfaces, biomaterials, cell biology, substrates.
Introduction An important goal of materials science is the development of interfaces that integrate the functions of living cells and materials. The development of materials that serve as substrates for adherent cells is important in a range of basic and applied programs.1 In basic research, substrates are used to study the adhesion of cells to the extracellular matrix (the protein scaffold that serves to organizes cells in tissue) and the processes by which this matrix directs cell function. In applied programs, materials are used to direct tissue compatibility in biomaterials and are now undergoing development to direct the differentiation of stem cells. A significant effort during the past 20 years has produced a variety of methods for modifying the surfaces of materials to promote cell adhesion.2 These methods are mostly based on modifying materials with polymers or self-assembled monolayers that in turn provide ligands that promote the adhesion of cells. Ligands are either directly immobilized on the modifying layers or are introduced indirectly when proteins in the contacting biological fluid adsorb to the surface. In both cases, cell adhesion is mediated by the interaction between receptors on the cell surface and peptide ligands on the material (Figure 1). Further, many researchers have contributed methods that can pattern the immobilization of ligands and therefore exert control over the shapes, sizes, and positions of cells on a substrate.3 Hence, it is now reasonably straightforward to modify the properties of
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a broad range of materials to provide cell adhesion. But these tailored interfaces fail to capture many of the important properties of the interface that joins a cell to its environment. In particular, the interactions between cells and the protein matrix are highly dynamic and undergo biochemical modifications to alter the ligands displayed to a cell and the mechanical properties of the matrix, both of which are important in influencing the activities of the cells. The development of dynamic, synthetic substrates that can similarly alter the ligands presented to a cell would provide unprecedented opportunities in fundamental cell biology. Further, the development of materials that can modulate cell adhesion (by directing cell growth, organizing multiple cell types into complex patterns, and releasing cultured cells) would have immediate application in tissue engineering and other cel
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