Fig. 1. (Color online) Microengineered synthetic substrates for cell/tissue mechanics studies. The properties of a substratum can be modified to adjust the cell/material interactions, such as surface topographies, stiffness, and adhesiveness. In addition, mechanical probes can be integrated into the substrate to detect the force in tissue. These include microbeads in the traction force microscopy and elastomeric micro-pillars.

Fig. 2. (Color online) Molecular dynamics at adhesion complexes. The actin network as a mechanosensitive machine connecting the cell to its substrate and neighbors. The building of a stable focal adhesion (FA) complex for cell–substrate adhesion. Actomyosin forces apply on the FA at a fixed speed and the rate of force increase in the complex increases proportionally with the ECM stiffness. To avoid the destabilization and detachment of the FA, the binding-unbinding dynamics of the transmembrane protein, integrin, that connects the cells to the substrate needs to be equal to the force loading rate in the complex. Another force buffer and mechanosensor in the complex is Talin. Its unfolding at ~ 10 pN at the normal rate of force loading in cells lead to vinculin binding to recruit more actin fibers, thus reinforcing the FA.

Fig. 3. (Color online) Methods for patterning adhesive surfaces. Semiconductor-based technologies has allowed the development of micro-contact printing and micro-stenciling for patterning biomolecules with define shapes. Later, researchers developed other techniques for this purpose, including Dip-pen lithography and UV-based patterning.

Fig. 4. (Color online) Methods for engineering substrate elasticity and viscosity. Conventionally, by controlling the cross-linking degree in elastomers, one could adjust the viscoelasticity of a gel. Another approach to change substrate rigidity involving photolithography is to pattern pillars of different shapes.

Fig. 5. (Color online) Topography cues influences cell adhesion and migration. (a) Scanning electron micrographs (SEMs) showing cells aligned to the nano-lines (Reproduced from Ref. [63]). (b) 3D confinement, such as microtubes, leads to amoeboid-like migration mode in neural stem cells (Reproduced from Ref. [38]).

Fig. 6. (Color online) Shear stress influences cell adherens junction (AJ) and filopodia protrusion. (a) At AJs, a higher force transmitted from F-actin caused by other factors (such as shear) leads to α-catenin unfolding and subsequently the recruitment of vinculin to stabilize the AJ structure. (b) SEMs showing filopodia formation in human cancer cells in response to wall shear stress (WSS) (Reproduced from Ref. [80]).