Matrix stiffness-regulated cell functions under different dimensionalities
Various cues from microenvironment that cell lives can regulate cell functions. In addition to biochemical cues, increasing evidence has demonstrated that mechanical cues (namely, stiffness of substrate/matrix in this review) presented by cell microenvironment are also critically important in regulating cell functions. However, most studies on stiffness-regulated cell functions have been mainly focused on 2D condition, which might cannot recapitulate the 3D microenvironment that cell encounters with in vivo. In contrast to 2D microenvironment, researches have already found that cell responds differently to mechanical cues under 3D microenvironment. In this review, the mechanisms of cell mechanosensing and mechanotransduction are briefly presented, followed by an introduction of the most studied 2D/3D platforms. The effects of substrate/matrix stiffness on cell functions, including cell migration, spreading, proliferation, phenotype, and differentiation, under different dimensionalities are summarized and discussed. Finally, the remained questions and future outlooks are also recommended.