PMID- 20418863 OWN - NLM STAT- MEDLINE DCOM- 20100707 LR - 20220331 IS - 1476-4660 (Electronic) IS - 1476-1122 (Print) IS - 1476-1122 (Linking) VI - 9 IP - 6 DP - 2010 Jun TI - Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate. PG - 518-26 LID - 10.1038/nmat2732 [doi] AB - 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. FAU - Huebsch, Nathaniel AU - Huebsch N AD - School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA. FAU - Arany, Praveen R AU - Arany PR FAU - Mao, Angelo S AU - Mao AS FAU - Shvartsman, Dmitry AU - Shvartsman D FAU - Ali, Omar A AU - Ali OA FAU - Bencherif, Sidi A AU - Bencherif SA FAU - Rivera-Feliciano, Jose AU - Rivera-Feliciano J FAU - Mooney, David J AU - Mooney DJ LA - eng GR - R37 DE013033/DE/NIDCR NIH HHS/United States GR - R37 DE013033-13/DE/NIDCR NIH HHS/United States GR - TL1 EB008540/EB/NIBIB NIH HHS/United States GR - 1TL1EB008540-01/EB/NIBIB NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20100425 PL - England TA - Nat Mater JT - Nature materials JID - 101155473 RN - 0 (Alginates) RN - 0 (Hydrogels) RN - 0 (Integrins) SB - IM CIN - Cell Stem Cell. 2010 Jun 4;6(6):499-501. PMID: 20569684 MH - Alginates MH - Animals MH - Biomechanical Phenomena MH - Biophysics MH - Cell Culture Techniques MH - Cell Transplantation/physiology MH - Extracellular Matrix/*physiology/ultrastructure MH - Humans MH - Hydrogels MH - Integrins/physiology MH - Mesenchymal Stem Cells/*cytology/*physiology MH - Microscopy/methods MH - Osteogenesis/physiology MH - Stem Cells/*cytology/*physiology PMC - PMC2919753 MID - NIHMS183313 EDAT- 2010/04/27 06:00 MHDA- 2010/07/08 06:00 PMCR- 2010/12/01 CRDT- 2010/04/27 06:00 PHST- 2009/09/24 00:00 [received] PHST- 2010/02/26 00:00 [accepted] PHST- 2010/04/27 06:00 [entrez] PHST- 2010/04/27 06:00 [pubmed] PHST- 2010/07/08 06:00 [medline] PHST- 2010/12/01 00:00 [pmc-release] AID - nmat2732 [pii] AID - 10.1038/nmat2732 [doi] PST - ppublish SO - Nat Mater. 2010 Jun;9(6):518-26. doi: 10.1038/nmat2732. Epub 2010 Apr 25.