Soft substrate and decreased cytoskeleton contractility promote coupling and morphology maintenance of pluripotent stem cells

The mechanical microenvironment affects the morphology and mechanical properties of cells, and it also plays an important role in cell functions. Pluripotent stem cells (PSCs) grow as multicellular colonies, and the coupling effects of cell–cell and cell-extracellular matrix interactions are complex but necessary for the formations and functions of tissues. This paper uses the finite element method to establish a three-dimensional calculation model of a pair of deformed PSCs in contact with each other and considers the growth and depolymerization of actin filaments. Then the effects of substrate stiffness on the morphology of cells and nuclei and the rearrangement of cytoskeleton are demonstrated. As the substrate becomes softer, the nuclei become loose and round, and the actin filaments will be assembled at a lower level, which could promote the formation of compacted cell colony while having a positive effect on maintaining pluripotency and inducing reprogramming efficiency. In addition, stronger activation of cytoskeleton contractility will compress the cytoplasm and nuclei. The cell mechanics model proposed in this paper provides a strategy for studying the cell morphology and cytoskeleton response of the two-cell system under different biophysical stimuli, and also lays the foundation for the further research on more mechanical factors of cell pluripotency. Graphic abstract: [Figure not available: see fulltext.].