Fig. 3 |. Cell-matrix interactions.

a | The matrix microenvironment influences cellular behaviour by cell-matrix interactions established by cell-adhesive ligands bound to cell-surface receptors, by the mechanical properties of the matrix (for example, stiffness) and by the degradability of the matrix. b | The 3D geometry of the matrix can be described by the relative pore or mesh size compared with the cell size. Matrix geometry defines the nature of cell-matrix contacts and how a cell senses other matrix properties, such as cell-adhesive ligands or mechanical properties. Fibrous matrices, for example, natural extracellular matrix and biomaterials such as collagen, have a pore size on approximately the scale of cells. Highly crosslinked hydrogels, such as polyethylene glycol hydrogels, have mesh sizes much smaller than the scale of a cell, which can inhibit cell growth and migration in the absence of degradability. Macroporous materials have large pores that can be on the scale of a cell or larger. c | Viscoelastic materials, for example, native extracellular matrix, display stress-relaxation behaviour. Upon application of stress to the matrix, the molecules rearrange to dissipate the stress over time. By contrast, elastic materials cannot dissipate stress. Plotting normalized stress versus time of a stress-relaxing material and an elastic material under constant strain shows that the stress in a stress-relaxing material decreases over time, whereas it remains constant in an elastic material. d | In materials with stress-stiffening behaviour, an applied stress (σ) that is greater than the characteristic critical stress point (σ_c) leads to stiffening of the material, owing to local molecular stretching. The modulus of a non-stiffening material remains the same regardless of the applied stress, whereas the modulus of a stress-stiffening material increases once σ > σ_c.