Engineering endothelial cell behavior via cell-surface interactions with chemically-defined nanoscale adhesion sites

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Slater, John Hundley, 1978-

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Current biomaterials are designed to be passive in nature to prevent the initiation of adverse immune responses upon contact with biological substances. While this approach of inertness is still a crucial design component for some applications, the possibility of engineering desired cell responses in the local environment of the material exists and is of particular interest in implantable devices and tissue engineered constructs. Fundamental knowledge of the relationships between cell adhesion and gross cell behavior will provide key design criteria for the creation of advanced biomaterials that induced locally controlled cellular responses. This work investigates the possibility of engineering cell behavior by limiting adhesion site maturation. Chemically-defined nanoislands of fibronectin were created using a combination of nanosphere lithography and an orthogonal surface functionalization strategy. Investigation of the adhesive and cytoskeletal components of cells cultured on these surfaces demonstrates that chemically-defined nanopatterns provide an upper size limit to adhesion site growth which in turn influences the degree of cytoskeletal formation. The imposed restriction on adhesion site growth results in the formation of a relatively higher number of more evenly distributed, small adhesions throughout the cell body. The adhesive behavior can be tuned by changing the nanopattern properties with respect to their size, spacing, and density. Furthermore, it is demonstrated that the observed differences in cell adhesion as imposed by the nanopatterned surfaces induces changes in gross cell behavior with respect to spreading, proliferation, and motility. The results presented here parallel observations documented in cells cultured on elastic surfaces and indicate that intracellular signaling cascades initiated and governed by cellular adhesion sites are sensitive to adhesion size/maturation and possibly the amount of force generated locally at these adhesion sites. The conclusions drawn from these studies give insight into the possibility of implementing nanostructured biomaterials for cell engineering purposes and provide design criteria for the next generation of tissue engineered constructs.




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