title: Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate.
abstract: Stem cells sense and respond to the mechanical properties of the extracellular matrix. However, both the extent to which extracellular-matrix mechanics affect stem-cell fate in three-dimensional microenvironments and the underlying biophysical mechanisms are unclear. We demonstrate that the commitment of mesenchymal stem-cell populations changes in response to the rigidity of three-dimensional microenvironments, with osteogenesis occurring predominantly at 11-30 kPa. In contrast to previous two-dimensional work, however, cell fate was not correlated with morphology. Instead, matrix stiffness regulated integrin binding as well as reorganization of adhesion ligands on the nanoscale, both of which were traction dependent and correlated with osteogenic commitment of mesenchymal stem-cell populations. These findings suggest that cells interpret changes in the physical properties of adhesion substrates as changes in adhesion-ligand presentation, and that cells themselves can be harnessed as tools to mechanically process materials into structures that feed back to manipulate their fate.
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Huebsch
authors.forename: Praveen R
authors.initials: PR
authors.lastname: Arany
authors.forename: Angelo S
authors.initials: AS
authors.lastname: Mao
authors.forename: Dmitry
authors.initials: D
authors.lastname: Shvartsman
authors.forename: Omar A
authors.initials: OA
authors.lastname: Ali
authors.forename: Sidi A
authors.initials: SA
authors.lastname: Bencherif
authors.forename: José
authors.initials: J
authors.lastname: Rivera-Feliciano
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D000464:Alginates; D000818:Animals; D001696:Biomechanical Phenomena; D001703:Biophysics; D018929:Cell Culture Techniques; D017690:Cell Transplantation / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D020100:Hydrogels; D016023:Integrins / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D008853:Microscopy / Q000379:methods; D010012:Osteogenesis / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*
chemical_list: D000464:Alginates; D020100:Hydrogels; D016023:Integrins