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Cell properties and functions, such as adhesion, migration, proliferation, differentiation, organization, protein expression and death, are dynamically regulated at the surface of cell membranes by interaction between a ligand molecule of cellular microenvironments and the membrane protein receptors. Furthermore, physical signals of cellular microenvironments, stiffness, elasticity and hydration, are also important factors for modulation of cellular functions. In the body, natural extracellular matrices (ECMs) and ECM-bound growth factors regulate the cell functions. The universal control of cell functions at the single-cell level through artificial modulation of extracellular microenvironments by mimicking the natural ECMs could be a key technique for biomedical fields. In this chapter, fabrication of nanometer-sized artificial ECM films using various polymers and proteins on single-cell surfaces to control cell functions is described. The thickness, charge, and components of the ECM films significantly affected cell functions. The optimized ECM films induced cell-cell organization to construct three-dimensional (3D) human tissue chips. Moreover, construction of 3D human tissue chips assisted with preparation of nano-ECM films on cell surface was performed automatically by an inkjet cell and protein printing system. Control of extracellular microenvironments using a nanometer-sized polymer/protein film as an artificial ECM could be useful as a novel technique to regulate cell properties and functions as desired.

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