Interplay of Matrix Stiffness and Cell–Cell Contact in Regulating Differentiation of Stem Cells

Abstract

Stem cells are capable of sensing and responding to the mechanical properties of extracellular matrixes (ECMs). It is well-known that, while osteogenesis is promoted on the stiff matrixes, adipogenesis is enhanced on the soft ones. Herein, we report an "abnormal" tendency of matrix-stiffness-directed stem cell differentiation. Well-defined nanoarrays of cell-adhesive arginine-glycine-aspartate (RGD) peptides were modified onto the surfaces of persistently nonfouling poly(ethylene glycol) (PEG) hydrogels to achieve controlled specific cell adhesion and simultaneously eliminate nonspecific protein adsorption. Mesenchymal stem cells were cultivated on the RGD-nanopatterned PEG hydrogels with the same RGD nanospacing but different hydrogel stiffnesses and incubated in the induction medium to examine the effect of matrix stiffness on osteogenic and adipogenic differentiation extents. When stem cells were kept at a low density during the induction period, the differentiation tendency was consistent with the previous reports in the literature; however, both lineage commitments were favored on the stiff matrices at a high cell density. We interpreted such a complicated stiffness effect at a high cell density in two-dimensional culture as the interplay of matrix stiffness and cell-cell contact. As a result, this study strengthens the essence of the stiffness effect and highlights the combinatory effects of ECM cues and cell cues on stem cell differentiation.

Effects of substrate stiffness and cell-cell contact on mesenchymal stem cell differentiation

“…Understanding the factors influencing their differentiation in vitro is of major therapeutic interest. Cell-cell contact and mechanical properties of the substrate have been shown to be two important factors affecting MSC differentiation, but their interplay has received little attention [2]. In a cytoskeleton and integrin-mediated mechanism, mesenchymal stem cells (MSCs) will respond to substrate stiffnesses by differentiating down specific lineages [3–6].…”

Left‐Right Symmetry or Asymmetry of Cells on Stripe‐Like Micropatterned Material Surfaces

“…In this study, we examined rat mesenchymal stem cells (rMSCs), human mesenchymal stem cells (hMSCs), human foreskin fibroblasts (HFFs), and human umbilical vascular endothelial cells (HUVECs). In particular, rMSCs have been much investigated in the literature, [62][63][64][65] and will be paid the most attention to in this study because rMSCs exhibited the leftright asymmetry. Even for such a cell type, the asymmetry occurred only with a relative probability instead of an absolute chirality as definite as L-and R-configuration of an optically chiral molecule.…”

Persistent Photoconductivity, Nanoscale Topography, and Chemical Functionalization Can Collectively Influence the Behavior of PC12 Cells on Wide Bandgap Semiconductor Surfaces

“…In addition, fabrication procedures such as soft‐lithographic protocols can often be tailored to accommodate modulation of surface chemistry . As a result, the creation of 2D biological interfaces with desired morphological and chemical characteristics have become essential tools for diverse groups of researchers . The collective efforts of many scientists have shown how to manipulate different classes of materials to accommodate the advancement of inorganic‐biomolecular‐cellular modalities.…”