(a) Design of microenvironments that capture the features of 3-D culture. Micropatterned substrates are presented to precisely control the cell shape and cytoskeletal architecture (b) as well as multicellular organization, without altering the physical or chemical attributes of the microenvironment. (c) Arrays of silicon posts of sub-micrometer diameter are used to study the effects of ECM sitffness on tumor cells. (d) Similary, numerous designer hydrogel systems can be differentially crosslinked to alter substrate stiffness and used to study the effects of ECM sitffness on cells. (e) and (f) Nanotopographic posts are also designed to sustain the size and geomery of cell-matrix adhesions. (g) and (h) In addition, microfluidic devices by which the soluble enviroment can be stringently defined for polarization study, migration, and chemotaxis of tumor cells under gradients are also designed.^[97]