Schematic diagrams of various methods to apply biophysical signals to cells. (A) Manipulation of substrate stiffness by (i) tuning the rigidity of the materials or (ii) using micro-post array with different height to adjust the rigidity. (B) Confinement of cell shape by patterning extracellular matrix protein such as fibronectin onto the substrate. Area outside the patterned shape will be coated with anti-fouling reagent to prevent cell adhesion. (C) Modification of surface topography. (D) Application of external forces, such as compression by compressing the substrate, tension by stretching the substrate, or shear stress by fluid flow.