The Effect of Cell Contractility and Packing on Extracellular Matrix and Soft Tissue Rheology

In the past decades it has become clear that the mechanical properties of tissues are important for healthy functioning. The mechanical properties of tissues and their load-bearing components found in the extracellular matrix (ECM) have been tested mechanically to provide more insight. However, there is a discrepancy between tissue and ECM mechanics. In this thesis this discrepancy is investigated with a novel multiaxial rheology method, which addresses a physiologically relevant combination of shear and axial strains. Blood clots are used to study the effect of cell traction and cell packing on ECM mechanics. The results show that ECM networks compression soften and extension stiffen in a typical asymmetric manner. The apparent Young’s moduli and shear moduli are decoupled, and are strongly influenced by a modest degree of axial strain. Cell traction induced pre-stress does not change the direction of this response but makes it more symmetrical and increases shear moduli. Close red cell packing in blood clots reverses the behavior of the clots from compression softening to stiffening, and from extension and shear strain stiffening to softening, resembling soft tissues. The same effects can be mimicked by embedding chemically inert beads into a fibrin network at densities approaching the jamming threshold for granular and colloidal materials. The overall conclusion is that cell jamming is likely to be the determining factor of soft tissue mechanics. This has implications for the understanding of tissue mechanics in physiological and pathological situations as well as the modeling of tissues