Interplay of Matrix Stiffness and Protein Tethering in Stem Cell Differentiation

Overview

Journal Nat Mater

Date 2014 Aug 11

PMID 25108614

Citations 370

Authors

Jessica H Wen

Ludovic G Vincent

Alexander Fuhrmann

Yu Suk Choi

Kolin C Hribar

Hermes Taylor-Weiner

Shaochen Chen

Adam J Engler

Affiliations

Soon will be listed here.

Abstract

Stem cells regulate their fate by binding to, and contracting against, the extracellular matrix. Recently, it has been proposed that in addition to matrix stiffness and ligand type, the degree of coupling of fibrous protein to the surface of the underlying substrate, that is, tethering and matrix porosity, also regulates stem cell differentiation. By modulating substrate porosity without altering stiffness in polyacrylamide gels, we show that varying substrate porosity did not significantly change protein tethering, substrate deformations, or the osteogenic and adipogenic differentiation of human adipose-derived stromal cells and marrow-derived mesenchymal stromal cells. Varying protein-substrate linker density up to 50-fold changed tethering, but did not affect osteogenesis, adipogenesis, surface-protein unfolding or underlying substrate deformations. Differentiation was also unaffected by the absence of protein tethering. Our findings imply that the stiffness of planar matrices regulates stem cell differentiation independently of protein tethering and porosity.

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References

Bangasser B, Rosenfeld S, Odde D . Determinants of maximal force transmission in a motor-clutch model of cell traction in a compliant microenvironment. Biophys J. 2013; 105(3):581-92. PMC: 3736748. DOI: 10.1016/j.bpj.2013.06.027. View

Khatiwala C, Peyton S, Metzke M, Putnam A . The regulation of osteogenesis by ECM rigidity in MC3T3-E1 cells requires MAPK activation. J Cell Physiol. 2007; 211(3):661-72. DOI: 10.1002/jcp.20974. View

Rowlands A, George P, Cooper-White J . Directing osteogenic and myogenic differentiation of MSCs: interplay of stiffness and adhesive ligand presentation. Am J Physiol Cell Physiol. 2008; 295(4):C1037-44. DOI: 10.1152/ajpcell.67.2008. View

Choi Y, Vincent L, Lee A, Kretchmer K, Chirasatitsin S, Dobke M . The alignment and fusion assembly of adipose-derived stem cells on mechanically patterned matrices. Biomaterials. 2012; 33(29):6943-51. PMC: 3408879. DOI: 10.1016/j.biomaterials.2012.06.057. View

Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M . Role of YAP/TAZ in mechanotransduction. Nature. 2011; 474(7350):179-83. DOI: 10.1038/nature10137. View

Chopra A, Lin V, McCollough A, Atzet S, Prestwich G, Wechsler A . Reprogramming cardiomyocyte mechanosensing by crosstalk between integrins and hyaluronic acid receptors. J Biomech. 2011; 45(5):824-31. PMC: 3386849. DOI: 10.1016/j.jbiomech.2011.11.023. View

Choi Y, Vincent L, Lee A, Dobke M, Engler A . Mechanical derivation of functional myotubes from adipose-derived stem cells. Biomaterials. 2011; 33(8):2482-91. PMC: 3261363. DOI: 10.1016/j.biomaterials.2011.12.004. View

Kaushik G, Zambon A, Fuhrmann A, Bernstein S, Bodmer R, Engler A . Measuring passive myocardial stiffness in Drosophila melanogaster to investigate diastolic dysfunction. J Cell Mol Med. 2012; 16(8):1656-62. PMC: 3326184. DOI: 10.1111/j.1582-4934.2011.01517.x. View

Fu J, Wang Y, Yang M, Desai R, Yu X, Liu Z . Mechanical regulation of cell function with geometrically modulated elastomeric substrates. Nat Methods. 2010; 7(9):733-6. PMC: 3069358. DOI: 10.1038/nmeth.1487. View

10.

Engler A, Bacakova L, Newman C, Hategan A, Griffin M, Discher D . Substrate compliance versus ligand density in cell on gel responses. Biophys J. 2003; 86(1 Pt 1):617-28. PMC: 1303831. DOI: 10.1016/S0006-3495(04)74140-5. View

11.

Pelham Jr R, Wang Y . Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci U S A. 1998; 94(25):13661-5. PMC: 28362. DOI: 10.1073/pnas.94.25.13661. View

12.

Plotnikov S, Pasapera A, Sabass B, Waterman C . Force fluctuations within focal adhesions mediate ECM-rigidity sensing to guide directed cell migration. Cell. 2012; 151(7):1513-27. PMC: 3821979. DOI: 10.1016/j.cell.2012.11.034. View

13.

Bonanni B, Kamruzzahan A, Bizzarri A, Rankl C, Gruber H, Hinterdorfer P . Single molecule recognition between cytochrome C 551 and gold-immobilized azurin by force spectroscopy. Biophys J. 2005; 89(4):2783-91. PMC: 1366778. DOI: 10.1529/biophysj.105.064097. View

14.

Huebsch N, Arany P, Mao A, Shvartsman D, Ali O, Bencherif S . Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate. Nat Mater. 2010; 9(6):518-26. PMC: 2919753. DOI: 10.1038/nmat2732. View

15.

McBeath R, Pirone D, Nelson C, Bhadriraju K, Chen C . Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 2004; 6(4):483-95. DOI: 10.1016/s1534-5807(04)00075-9. View

16.

Holle A, Tang X, Vijayraghavan D, Vincent L, Fuhrmann A, Choi Y . In situ mechanotransduction via vinculin regulates stem cell differentiation. Stem Cells. 2013; 31(11):2467-77. PMC: 3833960. DOI: 10.1002/stem.1490. View

17.

Chirasatitsin S, Engler A . Detecting cell-adhesive sites in extracellular matrix using force spectroscopy mapping. J Phys Condens Matter. 2010; 22(19):194102. PMC: 2997741. DOI: 10.1088/0953-8984/22/19/194102. View

18.

Del Alamo J, Meili R, Alvarez-Gonzalez B, Alonso-Latorre B, Bastounis E, Firtel R . Three-dimensional quantification of cellular traction forces and mechanosensing of thin substrata by fourier traction force microscopy. PLoS One. 2013; 8(9):e69850. PMC: 3762859. DOI: 10.1371/journal.pone.0069850. View

19.

Fuhrmann A, Anselmetti D, Ros R, Getfert S, Reimann P . Refined procedure of evaluating experimental single-molecule force spectroscopy data. Phys Rev E Stat Nonlin Soft Matter Phys. 2008; 77(3 Pt 1):031912. DOI: 10.1103/PhysRevE.77.031912. View

20.

Smith M, Gourdon D, Little W, Kubow K, Eguiluz R, Luna-Morris S . Force-induced unfolding of fibronectin in the extracellular matrix of living cells. PLoS Biol. 2007; 5(10):e268. PMC: 1994993. DOI: 10.1371/journal.pbio.0050268. View