Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation

Abstract

Signals from the microenvironment around a cell are known to influence cell behavior. Material properties, such as biochemical composition and substrate stiffness, are today accepted as significant regulators of stem cell fate. The knowledge of how cell behavior is influenced by 3D geometric cues is, however, strongly limited despite its potential relevance for the understanding of tissue regenerative processes and the design of biomaterials. Here, the role of surface curvature on the migratory and differentiation behavior of human mesenchymal stem cells (hMSCs) has been investigated on 3D surfaces with well‐defined geometric features produced by stereolithography. Time lapse microscopy reveals a significant increase of cell migration speed on concave spherical compared to convex spherical structures and flat surfaces resulting from an upward‐lift of the cell body due to cytoskeletal forces. On convex surfaces, cytoskeletal forces lead to substantial nuclear deformation, increase lamin‐A levels and promote osteogenic differentiation. The findings of this study demonstrate a so far missing link between 3D surface curvature and hMSC behavior. This will not only help to better understand the role of extracellular matrix architecture in health and disease but also give new insights in how 3D geometries can be used as a cell‐instructive material parameter in the field of biomaterial‐guided tissue regeneration.

Periodic microstructures on bioactive glass surfaces enhance osteogenic differentiation of human mesenchymal stromal cells and promote osteoclastogenesis in vitro

“…In addition, it is obvious that the cells adhere to the groove walls, partially overspanning the grooves, as observed previously . Werner et al correlated overspanning and cytoskeletal forces with osteogenic differentiation, implying that the structures in our study might be able to support osteogenic differentiation as well …”

Evaluation of the Topographical Influence on the Cellular Behavior of Human Umbilical Vein Endothelial Cells

“…It was demonstrated that 1.8 μm convex microlens can induce differentiation of mesenchymal stem cells [34] and 10 μm convex and concave micro-structures influence the shape of human macrophages [70] . Large scale (250 – 750 μm) convex and concave lens substrates were shown to alter the cell migration [71] , adhesion and proliferation [72] of mesenchymal stem cells. It was speculated that such curved geometry leads to nucleus and cell membrane deformations, which influences the cellular behavior [71,72] .…”

“…Large scale (250 – 750 μm) convex and concave lens substrates were shown to alter the cell migration [71] , adhesion and proliferation [72] of mesenchymal stem cells. It was speculated that such curved geometry leads to nucleus and cell membrane deformations, which influences the cellular behavior [71,72] . However, none of the lens topography studies examined the influence on cellular behavior in terms of interaction with other cells such as monocytes.…”

Recapitulation of molecular regulators of nuclear motion during cell migration

“…They showed that deformed nucleus was rapidly recovered by actin cables around the nucleus. Therefore, these profound evidences demonstrate that the nucleus is a center of mechanotransduction by remodeling its intra-and extra-spaces [107] The karyoplasmic ratio, a ratio of nuclear volume to cell volume, is known to roughly remain constant in diverse cell growth conditions, genetic variations, and various stages of the cell cycle that could affect cell dimension and DNA content [108]. Therefore, nuclear volume change largely follows cell volume change [109].…”