Cell-matrix reciprocity in 3D culture models with nonlinear elasticity

Three-dimensional (3D) matrix models using hydrogels are powerful tools to understand and predict cell behavior. The interactions between the cell and its matrix, however is highly complex: the matrix has a profound effect on basic cell functions but simultaneously, cells are able to actively manipulate the matrix properties. This (mechano)reciprocity between cells and the extracellular matrix (ECM) is central in regulating tissue functions and it is fundamentally important to broadly consider the biomechanical properties of the in vivo ECM when designing in vitro matrix models. This manuscript discusses two commonly used biopolymer networks, i.e. collagen and fibrin gels, and one synthetic polymer network, polyisocyanide gel (PIC), which all possess the characteristic nonlinear mechanics in the biological stress regime. We start from the structure of the materials, then address the uses, advantages, and limitations of each material, to provide a guideline for tissue engineers and biophysicists in utilizing current materials and also designing new materials for 3D cell culture purposes.