Persistence of fan-shaped keratocytes is a matrix-rigidity-dependent mechanism that requires α5β1integrin engagement.
Despite the importance of matrix rigidity on cell functions, many aspects of the mechanosensing process in highly migratory cells remain elusive. Here, we studied the migration of highly motile keratocytes on culture substrates with similar biochemical properties and rigidities spanning the range between soft tissues (~kPa) and stiff culture substrates (~GPa). We show that morphology, polarization and persistence of motile keratocytes are regulated by the matrix stiffness over seven orders of magnitude, without changing the cell spreading area. Increasing the matrix rigidity leads to more F-actin in the lamellipodia and to the formation of mature contractile actomyosin fibers that control the cell rear retraction. Keratocytes remain rounded and form nascent adhesions on compliant substrates, whereas large and uniformly distributed focal adhesions are formed on fan-shaped keratocytes migrating on rigid surfaces. By combining poly-L-lysine, fibronectin and vitronectin coatings with selective blocking of αvβ3or α5β1integrins, we show that αVβ3integrins permit the spreading of keratocytes but are not sufficient for polarization and rigidity sensing that require the engagement of α5β1integrins. Our study demonstrates a matrix rigidity-dependent regulation of the directional persistence in motile keratocytes and refines the role of αvβ3and α5β1integrins in the molecular clutch model.
Mechanobiology &Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium.
Maryam
M
Riaz
Mechanobiology &Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium.
Marie
M
Versaevel
Mechanobiology &Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium.
Danahe
D
Mohammed
Institute of Condensed Matter &Nanosciences, Bio &Soft Matter division, Universite Catholique de Louvain, Croix du Sud 1, box L7.04.02, B-1348 Louvain-la-Neuve, Belgium.
Karine
K
Glinel
Mechanobiology &Soft Matter Group, Laboratoire Interfaces et Fluides Complexes, Centre d'Innovation et de Recherche en Matériaux Polymères (CIRMAP), Research Institute for Biosciences, Université de Mons, 20, Place du Parc, B-7000 Mons, Belgium.
Sylvain
S
Gabriele
Science. 2005 Nov 18;310(5751):1139-43
16293750
J Cell Biol. 2007 Sep 24;178(7):1207-21
17893245
PLoS Biol. 2011 May;9(5):e1001059
21559321
Dev Cell. 2010 Aug 17;19(2):194-206
20708583
J Cell Biol. 2010 Jan 25;188(2):287-97
20100912
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):E1361-70
23515331
J Cell Sci. 1991 Jun;99 ( Pt 2):419-30
1885678
Nat Cell Biol. 2011 Nov 13;13(12):1457-65
22081092
FEBS Lett. 2013 Mar 18;587(6):763-9
23395612
J Cell Biol. 1998 Apr 6;141(1):1-4
9531543
Nat Cell Biol. 2016 Jan;18(1):54-64
26641717
PLoS One. 2008 Sep 18;3(9):e3234
18800171
Biomaterials. 2012 Oct;33(28):6672-81
22738780
Nat Mater. 2012 May 27;11(7):642-9
22635042
Biophys J. 2006 Mar 15;90(6):2213-20
16387786
Annu Rev Biochem. 2004;73:209-39
15189141
Biophys J. 2000 Jul;79(1):144-52
10866943
Cell. 2003 Feb 21;112(4):453-65
12600310
Curr Biol. 2013 Aug 5;23(15):1409-17
23831292
Biophys J. 2013 Aug 6;105(3):581-92
23931306
Microsc Res Tech. 1998 Dec 1;43(5):412-9
9858338
Nature. 2008 May 22;453(7194):475-80
18497816
Annu Rev Cell Dev Biol. 2010;26:315-33
19575647
Nat Mater. 2014 Oct;13(10):979-87
25108614
Nat Cell Biol. 2014 Mar;16(3):217-23
24561621
Am J Physiol Cell Physiol. 2002 Mar;282(3):C606-16
11832346
Sci Rep. 2015 Mar 30;5:9475
25820512
Sci Rep. 2014 Dec 08;4:7362
25482017
Physiol Rev. 2008 Apr;88(2):489-513
18391171
Cell. 2006 Nov 17;127(4):679-95
17110329
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13661-5
9391082
J Cell Sci. 2003 Apr 15;116(Pt 8):1397-408
12640025
Methods Cell Biol. 2014;121:33-48
24560501
J Cell Biol. 1986 Apr;102(4):1384-99
2420807
Cell. 2002 Sep 20;110(6):673-87
12297042
Nat Rev Mol Cell Biol. 2010 Sep;11(9):633-43
20729930
Cell. 1996 Feb 9;84(3):359-69
8608589
Nat Rev Mol Cell Biol. 2009 Jul;10(7):445-57
19546857
Science. 2008 Dec 12;322(5908):1687-91
19074349
Biophys J. 2007 Dec 15;93(12):4453-61
18045965
Sci Rep. 2016 Mar 18;6:23258
26987342
IUBMB Life. 2009 Jul;61(7):731-8
19514020
Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16245-50
19805288
J Cell Biol. 2005 May 9;169(3):515-26
15866889
Curr Opin Cell Biol. 2013 Oct;25(5):543-9
23726023
Curr Biol. 2011 Dec 20;21(24):2085-91
22137472
Lab Chip. 2013 Mar 7;13(5):777-80
23334710
Nat Rev Cancer. 2010 Jan;10(1):9-22
20029421
J Cell Sci. 1989 Jan;92 ( Pt 1):67-75
2476453
Cell. 2012 Dec 21;151(7):1513-27
23260139
Nat Rev Mol Cell Biol. 2014 Dec;15(12):813-24
25355506
J Cell Biol. 2001 Jun 11;153(6):1175-86
11402062
Eur Biophys J. 2011 Sep;40(9):1013-27
21833780
Nature. 1997 Feb 6;385(6616):537-40
9020360
J Struct Biol. 2003 Jun;142(3):327-33
12781659