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It is widely accepted that stem cells directly sense the elasticity of two-dimensional (2-D) substrates and differentiate into a distinct cell type dependent on the substrate elasticity ( direct-sensing differentiation : soft and hard substrates promote differentiation into soft and hard tissue lineage, respectively). Biologically, native extracellular matrices (ECMs) are constantly remodeled through out the life of individuals, which inadvertently introduce changes of mechanical properties. Therefore,  direct-sensing differentiation  might not fully take into account the responses of stem cells in the actual ECMs microenvironment. Recent investigations in three-dimensional (3-D) cell culture environment suggested the inconsistency of  direct-sensing differentiation . Stem cells specifically differentiate not only by sensing the elasticity of materials but also by considering the cellular traction exerted to reorganize the matrices and the matrices deformation. This paper aims to expand further how the cells incorporate the elasticity cues and traction-mediated deformation in final differentiation fates of stem cells. To achieve the aim, we introduced an empirical model based on the investigations in 3-D cell culture environment. The empirical model would serve as a useful framework for future studies intended to investigate the relationship of traction-mediated deformation and commitment of stem cells for variety of tissue lineage in 2-D or 3-D cell culture environment.

Physical cues of biomaterials guide stem cell fate of differentiation: The effect of elasticity of cell culture biomaterials