elicit phenotypes that are not expressed on conventionally rigid substrates. There is growing interest in controlling matrix stiffness, a concept that has led to discoveries in fields such as: Stem cell self-renewal Lineage specification Cancer cell phenotype Fibrosis Hepatocyte function Mechanosensing Cell culture in three dimensions Cell culture in three dimensions has been touted as "Biology's New Dimension". At present, the practice of cell culture remains based on varying combinations of single or multiple cell structures in 2D. Currently, there is an increase in use of 3D cell cultures in research areas including drug discovery, cancer biology, regenerative medicine, nanomaterials assessment and basic life science research. 3D cell cultures can be grown using a scaffold or matrix, or in a scaffold-free manner. Scaffold based cultures utilize an acellular 3D matrix or a liquid matrix. Scaffold-free methods are normally generated in suspensions. There are a variety of platforms used to facilitate the growth of three-dimensional cellular structures including scaffold systems such as hydrogel matrices and solid scaffolds, and scaffold-free systems such as low-adhesion plates, nanoparticle facilitated magnetic levitation, hanging drop plates, and rotary cell culture. Culturing cells in 3D leads to wide variation in gene expression signatures and partly mimics tissues in the physiological states. A 3D cell culture model showed cell growth similar to that of in vivo than did a monolayer culture, and all three cultures were capable of sustaining cell growth. As 3D culturing has been developed it turns out to have a great potential to design tumors models and investigate malignant transformation and metastasis, 3D cultures can provide aggerate tool for understanding changes, interactions, and cellular signaling. 3D cell culture in scaffolds Eric Simon, in a 1988 NIH SBIR grant report, showed that electrospinning could be used to produced nano- and submicron-scale polystyrene and polycarbonate fibrous scaffolds specifically intended for use as in vitro cell substrates. This early use of electrospun fibrous lattices for cell culture and tissue engineering showed that various cell types including Human Foreskin Fibroblasts (HFF), transformed Human Carcinoma (HEp-2), and Mink Lung Epithelium (MLE) would adhere to and proliferate upon polycarbonate fibers. It was noted that, as opposed to the flattened morphology typically seen in 2D culture, cells grown on the electrospun fibers exhibited a more histotypic rounded 3-dimensional morphology generally observed in vivo. 3D cell culture in hydrogels As the natural extracellular matrix (ECM) is important in the survival, proliferation, differentiation and