Cell-cell mechanical communication through compliant substrates.
The role of matrix mechanics on cell behavior is under intense investigation. Cells exert contractile forces on their matrix and the matrix elasticity can alter these forces and cell migratory behavior. However, little is known about the contribution of matrix mechanics and cell-generated forces to stable cell-cell contact and tissue formation. Using matrices of varying stiffness and measurements of endothelial cell migration and traction stresses, we find that cells can detect and respond to substrate strains created by the traction stresses of a neighboring cell, and that this response is dependent on matrix stiffness. Specifically, pairs of endothelial cells display hindered migration on gels with elasticity below 5500 Pa in comparison to individual cells, suggesting these cells sense each other through the matrix. We believe that these results show for the first time that matrix mechanics can foster tissue formation by altering the relative motion between cells, promoting the formation of cell-cell contacts. Moreover, our data indicate that cells have the ability to communicate mechanically through their matrix. These findings are critical for the understanding of cell-cell adhesion during tissue formation and disease progression, and for the design of biomaterials intended to support both cell-matrix and cell-cell adhesion.
Reinhart-King
Cynthia A
CA
Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.
Dembo
Micah
M
Hammer
Daniel A
DA
D000818:Animals; D001696:Biomechanical Phenomena; D002417:Cattle; D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D013314:Stress, Mechanical
Science. 1980 Apr 11;208(4440):177-9
6987736
Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 2000 Sep;62(3 Pt B):3909-19
11088911
J Cell Biol. 1985 Dec;101(6):2330-4
3905825
Biophys J. 2005 Jul;89(1):676-89
15849250
J Cell Sci. 1991 Jun;99 ( Pt 2):419-30
1885678
Am J Physiol Cell Physiol. 2006 Jun;290(6):C1640-50
16407416
Agents Actions Suppl. 1983;12:14-33
6573115
J Cell Sci. 1976 Nov;22(2):371-83
1033939
Cell Motil Cytoskeleton. 2005 Jan;60(1):24-34
15573414
J Cell Sci. 1992 Jan;101 ( Pt 1):1-5
1569118
Biophys J. 2006 Mar 15;90(6):2213-20
16387786
Am J Physiol Cell Physiol. 2000 Nov;279(5):C1345-50
11029281
J Math Biol. 1988;26(3):263-98
3411255
J Cell Sci. 1998 Aug;111 ( Pt 16):2423-32
9683636
J Biol Chem. 1983 Feb 25;258(4):2340-9
6822565
Plast Reconstr Surg. 1998 Jul;102(1):124-31; discussion 132-4
9655417
Dev Biol. 2005 Feb 1;278(1):255-63
15649477
Nat Rev Cancer. 2003 May;3(5):362-74
12724734
Nature. 1980 Dec 4;288(5790):483-4
7442795
Biophys J. 2000 Jul;79(1):144-52
10866943
J Cell Physiol. 2005 Jul;204(1):198-209
15669099
J Cell Biol. 2005 Oct 10;171(1):153-64
16216928
J Neurosci. 2001 Aug 15;21(16):6159-69
11487639
Cancer Cell. 2005 Sep;8(3):241-54
16169468
Lab Invest. 1992 May;66(5):536-47
1374138
Biophys J. 2004 Oct;87(4):2818-27
15454473
Biophys J. 2002 Sep;83(3):1380-94
12202364
Biophys J. 1999 Apr;76(4):2307-16
10096925
Methods Enzymol. 1998;298:489-96
9751904
Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10889-94
16832052