Biomaterial design motivated by characterization of natural extracellular matrices
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Introduction Biological cells sense both the passive physical properties of their microenvironment as well as changes due to externally applied stress.1,2 One challenge to studying mechanobiology is that physical properties are often intertwined, and thus it can be difficult to identify specific effects of individual mechanical cues that are coupled in vivo. Thus, it is beneficial to investigate specific aspects of the microenvironment to assess their importance in regulation of cell function. An oft-used approach is to categorize cell microenvironment properties in groups such as biochemical, mechanical, and topographical3 (Figure 1). Biochemistry includes the molecular components that regulate specificity of interaction, for example between signaling molecules and their receptors, or between cell adhesion molecules and ligands within the extracellular matrix (ECM) or on adjacent cells. Mechanical properties that are sensed by cells include the viscoelastic properties of the microenvironment as well as imposed mechanical stress on cells.4–7 This is a complex area of mechanobiology since, for example, endothelial cells (cells that line blood vessels) and pulmonary epithelial cells (cells that line the lung) have dissimilar mechanical loading environments (i.e., shear stress and tissue stretch, respectively), and in other contexts such as cancer, tissue rigidity appears to contribute to disease progression.8,9 Finally, topographical cues result from a wide range of properties, including dimensionality and the spacing and density of adhesion ligands.10–13
Other microenvironmental factors such as matrix porosity and cell density can affect cell shape, which itself can control even the most basic of cell behaviors.14–17 While cells and the ECM that constitute tissues have been well studied from a biological perspective, a growing group of investigators now study this field from a new perspective through consideration of cells, matrices, and whole tissues as materials. The material properties at these different length scales define their physical stability and also provide instructive cues that maintain homeostasis in healthy tissues or drive dynamic events during development, wound healing, and disease progression. Through a materials science perspective, novel environments can be generated for in vitro investigation of cell function and for in vivo guidance of proper cell behavior. This review highlights the study of natural tissues as materials and the use of this information to develop novel synthetic materials that guide cell function. We specifically highlight studies on the material properties of two ECM components, fibronectin (Fn) and Type I collagen, and discuss how novel synthetic platforms allow control over these properties in order to control cell function.
Properties of natural tissues For determining design specifications for the material properties of synthetic materials or engineered cell culture surfaces that will be used for a particular application, one must first
Catherine K. Kuo, Department of Biomedical
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