Geometric constraint of mechanosensing by modification of hydrogel thickness prevents stiffness-induced differentiation in bone marrow stromal cells.

Autor: Hernandez-Miranda ML; Centre for Human Development, Stem Cells and Regenerative Medicine, Bone and Joint Research Group, Institute for Life Sciences, University of Southampton Faculty of Medicine , Southampton, UK., Xu D; Ningbo Institute of Technology, Beihang University , Ningbo 315800, People's Republic of China.; Bioengineering Science Research Group, University of Southampton Faculty of Engineering and Physical Sciences , Southampton, UK., Ben Issa AA; Centre for Human Development, Stem Cells and Regenerative Medicine, Bone and Joint Research Group, Institute for Life Sciences, University of Southampton Faculty of Medicine , Southampton, UK., Johnston DA; Biomedical Imaging Unit, University of Southampton Faculty of Medicine , Southampton, UK., Browne M; Bioengineering Science Research Group, University of Southampton Faculty of Engineering and Physical Sciences , Southampton, UK., Cook RB; Bioengineering Science Research Group, University of Southampton Faculty of Engineering and Physical Sciences , Southampton, UK., Sengers BG; Bioengineering Science Research Group, University of Southampton Faculty of Engineering and Physical Sciences , Southampton, UK., Evans N; Centre for Human Development, Stem Cells and Regenerative Medicine, Bone and Joint Research Group, Institute for Life Sciences, University of Southampton Faculty of Medicine , Southampton, UK.; Bioengineering Science Research Group, University of Southampton Faculty of Engineering and Physical Sciences , Southampton, UK.
Jazyk: angličtina
Zdroj: Journal of the Royal Society, Interface [J R Soc Interface] 2024 Oct; Vol. 21 (219), pp. 20240485. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1098/rsif.2024.0485
Abstrakt: Extracellular matrix (ECM) stiffness is fundamental in cell division, movement and differentiation. The stiffness that cells sense is determined not only by the elastic modulus of the ECM material but also by ECM geometry and cell density. We hypothesized that these factors would influence cell traction-induced matrix deformations and cellular differentiation in bone marrow stromal cells (BMSCs). To achieve this, we cultivated BMSCs on polyacrylamide hydrogels that varied in elastic modulus and geometry and measured cell spreading, cell-imparted matrix deformations and differentiation. At low cell density BMSCs spread to a greater extent on stiff compared with soft hydrogels, or on thin compared with thick hydrogels. Cell-imparted matrix deformations were greater on soft compared with stiff hydrogels or thick compared with thin hydrogels. There were no significant differences in osteogenic differentiation relative to hydrogel elastic modulus and thickness. However, increased cell density and/or prolonged culture significantly reduced matrix deformations on soft hydrogels to levels similar to those on stiff substrates. This suggests that at high cell densities cell traction-induced matrix displacements are reduced by both neighbouring cells and the constraint imposed by an underlying stiff support. This may explain observations of the lack of difference in osteogenic differentiation as a function of stiffness.
Databáze: MEDLINE