Why aren't tissues like biopolymer networks? Packing colloidal particles in a fibrous matrix.

The stiffness of tissues in which cells are embedded has effects on cell structure and function that can act independently of or override chemical stimuli. Rheologic measurements of liver, brain, and other soft tissues over a range of shear, compressive, and elongational strains show that the viscoelastic response of these tissues differs from that of synthetic hydrogels that have similar elastic moduli when measured in the linear range. The shear moduli of soft tissues generally decrease with increasing shear or elongational strain, but they strongly increase under uniaxial compression. In contrast, networks of crosslinked collagen or fibrin soften under compression, but strongly increase shear modulus when deformed in shear or extension. The compression softening of fibrous networks converts to compression stiffening characteristic of tissues as cells or cell-sized volume-conserving inert beads are incorporated into the fibrous networks at sufficiently high volume fractions. Compression stiffening in fibrous networks does not require the inclusions to become close packed or jammed, but the volume occupied by the cells or beads constrains the relaxation modes of the fibers to limit soft bending modes and enhance stiff stretching modes.