Elucidating the role of matrix stiffness in 3D cell migration and remodeling.
Reductionist in vitro model systems which mimic specific extracellular matrix functions in a highly controlled manner, termed artificial extracellular matrices (aECM), have increasingly been used to elucidate the role of cell-ECM interactions in regulating cell fate. To better understand the interplay of biophysical and biochemical effectors in controlling three-dimensional cell migration, a poly(ethylene glycol)-based aECM platform was used in this study to explore the influence of matrix cross-linking density, represented here by stiffness, on cell migration in vitro and in vivo. In vitro, the migration behavior of single preosteoblastic cells within hydrogels of varying stiffness and susceptibilities to degradation by matrix metalloproteases was assessed by time-lapse microscopy. Migration behavior was seen to be strongly dependent on matrix stiffness, with two regimes identified: a nonproteolytic migration mode dominating at relatively low matrix stiffness and proteolytic migration at higher stiffness. Subsequent in vivo experiments revealed a similar stiffness dependence of matrix remodeling, albeit less sensitive to the matrix metalloprotease sensitivity. Therefore, our aECM model system is well suited to unveil the role of biophysical and biochemical determinants of physiologically relevant cell migration phenomena.
Department of Cranio-Maxillofacial Surgery, University Hospital Zurich, Switzerland. martin.ehrbar@usz.ch
M
M
Ehrbar
A
A
Sala
P
P
Lienemann
A
A
Ranga
K
K
Mosiewicz
A
A
Bittermann
S C
SC
Rizzi
F E
FE
Weber
M P
MP
Lutolf
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D004548:Elasticity; D005109:Extracellular Matrix / Q000502:physiology*; D020100:Hydrogels / Q000737:chemistry; D020782:Matrix Metalloproteinases / Q000502:physiology*; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D020100:Hydrogels; D011092:Polyethylene Glycols; D020782:Matrix Metalloproteinases
Biomacromolecules. 2007 Oct;8(10):3000-7
17883273
Nat Biotechnol. 2005 Jan;23(1):47-55
15637621
Biomaterials. 2005 May;26(15):2467-77
15585249
J Biomed Mater Res A. 2005 Oct 1;75(1):73-88
16049978
Bioconjug Chem. 1999 Jan-Feb;10(1):75-81
9893967
Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5413-8
12686696
Langmuir. 2010 Jul 6;26(13):11127-34
20545368
Cell Stem Cell. 2008 Mar 6;2(3):205-13
18371446
Curr Opin Biotechnol. 2010 Oct;21(5):704-9
20638268
Biophys J. 2008 Apr 1;94(7):2914-25
18178662
Integr Biol (Camb). 2009 Mar;1(3):235-41
20023734
Acta Biomater. 2007 Sep;3(5):615-29
17572164
Biomacromolecules. 2003 May-Jun;4(3):713-22
12741789
J Cell Biol. 2009 Apr 6;185(1):11-9
19332889
Biophys J. 2005 Aug;89(2):1374-88
15923238
J Biomed Mater Res. 2002 Jan;59(1):63-72
11745538
J Cell Biol. 2003 Jan 20;160(2):267-77
12527751
Biomaterials. 2006 Oct;27(28):4881-93
16762407
Trends Biotechnol. 2008 Jul;26(7):382-92
18501452
FASEB J. 2002 May;16(7):751-3
11923220
Biotechnol Bioeng. 2009 Jul 1;103(4):655-63
19472329
Ann Biomed Eng. 2007 Jan;35(1):91-100
17080315
Nat Biotechnol. 2003 May;21(5):513-8
12704396
Biomaterials. 2007 Sep;28(26):3856-66
17568666
Cell Mol Life Sci. 2000 Jan 20;57(1):41-64
10949580
Bioconjug Chem. 2001 Nov-Dec;12(6):1051-6
11716699
J Cell Biol. 2010 Jan 11;188(1):11-9
19951899
Biomacromolecules. 2002 Jul-Aug;3(4):710-23
12099815
J Am Chem Soc. 2003 Nov 26;125(47):14298-9
14624577
Ann Biomed Eng. 2005 Nov;33(11):1469-90
16341917
Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10889-94
16832052
Biomaterials. 2003 Sep;24(21):3825-34
12818555
J Biomater Sci Polym Ed. 2008;19(5):543-72
18419938
J Cell Sci. 2009 Sep 15;122(Pt 18):3203-8
19726629