Robust organizational principles of protrusive biopolymer networks in migrating living cells.
Cell migration is associated with the dynamic protrusion of a thin actin-based cytoskeletal extension at the cell front, which has been shown to consist of two different substructures, the leading lamellipodium and the subsequent lamellum. While the formation of the lamellipodium is increasingly well understood, organizational principles underlying the emergence of the lamellum are just beginning to be unraveled. We report here on a 1D mathematical model which describes the reaction-diffusion processes of a polarized actin network in steady state, and reproduces essential characteristics of the lamellipodium-lamellum system. We observe a steep gradient in filament lengths at the protruding edge, a local depolymerization maximum a few microns behind the edge, as well as a differential dominance of the network destabilizer ADF/cofilin and the stabilizer tropomyosin. We identify simple and robust organizational principles giving rise to the derived network characteristics, uncoupled from the specifics of any molecular implementation, and thus plausibly valid across cell types. An analysis of network length dependence on physico-chemical system parameters implies that to limit array treadmilling to cellular dimensions, network growth has to be truncated by mechanisms other than aging-induced depolymerization, e.g., by myosin-associated network dissociation at the transition to the cell body. Our work contributes to the analytical understanding of the cytoskeletal extension's bisection into lamellipodium and lamellum and sheds light on how cells organize their molecular machinery to achieve motility.
Institute of Soft Matter Physics, University of Leipzig, Leipzig, Germany. stuhrmann@amolf.nl
Björn
B
Stuhrmann
Florian
F
Huber
Josef
J
Käs
D000818:Animals; D001704:Biopolymers / Q000378:metabolism*; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D005399:Fishes; D015603:Keratinocytes / Q000166:cytology*; D008962:Models, Theoretical; D020409:Molecular Motor Proteins / Q000737:chemistry; D011554:Pseudopodia / Q000737:chemistry* / Q000378:metabolism
D001704:Biopolymers; D020409:Molecular Motor Proteins
J Cell Biol. 2006 Sep 11;174(6):767-72
16966418
PLoS Biol. 2007 Nov;5(11):e317
18044991
Cell. 2003 Feb 21;112(4):453-65
12600310
J Cell Sci. 2007 Mar 15;120(Pt 6):1113-25
17327278
J Cell Sci. 2007 Oct 1;120(Pt 19):3475-87
17855386
Curr Biol. 2001 Aug 21;11(16):1300-4
11525747
J Math Biol. 2009 Jan;58(1-2):135-61
18488227
Proc Natl Acad Sci U S A. 2003 May 27;100(11):6337-42
12743368
Cell. 2008 May 30;133(5):841-51
18510928
J Cell Biol. 1997 Oct 20;139(2):397-415
9334344
Science. 2005 Nov 18;310(5751):1139-43
16293750
Nature. 1999 Oct 7;401(6753):613-6
10524632
J Cell Biol. 2005 Feb 14;168(4):619-31
15716379
J Cell Biol. 1997 Mar 24;136(6):1307-22
9087445
J Math Biol. 2001 Oct;43(4):325-55
12120872
Math Biosci. 1999 Mar 1;156(1-2):207-28
10204394
FEBS Lett. 2008 Jun 18;582(14):2086-92
18328266
Biophys J. 2003 Mar;84(3):1591-605
12609863
Mol Biol Cell. 2005 Feb;16(2):649-64
15548599
Eur Biophys J. 2006 Oct;35(8):713-9
16871382
Biophys J. 1996 Dec;71(6):3030-45
8968574
Multiscale Model Simul. 2005;3(2):413-439
19116671
Annu Rev Biophys Biomol Struct. 2000;29:545-76
10940259
EMBO J. 2008 Apr 9;27(7):982-92
18309290
Biophys J. 2010 Oct 6;99(7):2153-62
20923649
Annu Rev Biomed Eng. 2007;9:1-34
17461730
Biophys J. 2002 Sep;83(3):1237-58
12202352
Proc Natl Acad Sci U S A. 2010 May 18;107(20):9141-6
20439759
Curr Biol. 1999 Jan 14;9(1):11-20
9889119
J Biomech. 2009 Feb 9;42(3):297-302
19135203
Trends Cell Biol. 1999 Sep;9(9):364-70
10461190
J Biol Chem. 1990 Dec 5;265(34):21323-9
2250026
J Cell Biol. 2008 Jul 28;182(2):341-53
18663144
Trends Cell Biol. 2010 Nov;20(11):628-33
20833046
Biophys J. 1993 Jul;65(1):316-24
8369439
Mol Biol Cell. 2005 Feb;16(2):507-18
15548591
Dev Cell. 2007 Nov;13(5):646-662
17981134
Science. 2003 Apr 4;300(5616):142-5
12677069
J Biol Chem. 1991 Jan 5;266(1):1-4
1985885
Nat Cell Biol. 2008 Mar;10(3):306-13
18278037
Biophys J. 2007 Feb 1;92(3):744-68
17098793
J Cell Biol. 1999 May 31;145(5):1009-26
10352018
J Cell Sci. 2002 Dec 1;115(Pt 23):4649-60
12415009
J Cell Biol. 2007 May 7;177(3):465-76
17470633
Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9660-5
15210979
Science. 2004 Sep 17;305(5691):1782-6
15375270
J Cell Biochem. 2009 Dec 15;108(6):1252-62
19862699
Biophys J. 2008 Aug;95(4):1627-38
18502800
Biophys J. 2003 May;84(5):2907-18
12719223
Curr Opin Cell Biol. 2009 Feb;21(1):28-37
19168341
Biophys J. 2006 Jan 15;90(2):413-22
16258044
Biophys J. 2010 May 19;98(9):1893-901
20441753
J Cell Biol. 2002 Mar 18;156(6):1065-76
11901171
Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6304-9
20308581
J Cell Biol. 2002 Jul 8;158(1):31-7
12105180
Biophys J. 1998 Oct;75(4):2070-8
9746549
Mol Biol Cell. 2003 Nov;14(11):4667-75
13679520
Phys Rev Lett. 2007 Aug 3;99(5):058103
17930797
Curr Opin Cell Biol. 2005 Feb;17(1):62-6
15661520
Curr Opin Cell Biol. 2006 Feb;18(1):32-9
16318917
Mol Cell. 2006 Oct 6;24(1):13-23
17018289
Methods Cell Biol. 2008;84:911-37
17964954
Biophys J. 2009 Sep 2;97(5):1254-64
19720013
Biophys J. 1999 Sep;77(3):1721-32
10465781
J Mol Biol. 2008 Jan 11;375(2):325-30
18021803
Bull Math Biol. 2006 Jul;68(5):1169-211
16794915
Mol Biol Cell. 2005 Mar;16(3):1223-31
15635099
Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7086-91
17440042
Nature. 2003 Apr 17;422(6933):741-5
12700767
J Cell Biol. 2006 May 8;173(3):383-94
16651381
J Cell Biol. 1999 Apr 19;145(2):331-45
10209028
Trends Cell Biol. 2002 Mar;12(3):112-20
11859023
Nat Cell Biol. 2007 Oct;9(10):1110-21
17909522
Science. 2004 Apr 30;304(5671):743-6
15118165
Curr Biol. 2002 Aug 6;12(15):R523-5
12176375
Nat Cell Biol. 2006 Mar;8(3):215-26
16501565
Proc Natl Acad Sci U S A. 2005 May 31;102(22):7847-52
15911773
Biophys J. 2008 Dec 15;95(12):5508-23
18708450
Biophys J. 2004 Mar;86(3):1777-93
14990504
Curr Biol. 2007 Mar 6;17(5):395-406
17331727
Biochemistry. 1984 Dec 18;23(26):6631-41
6543322
J Cell Biol. 1996 Oct;135(1):169-79
8858171
J Cell Biol. 2001 Nov 12;155(4):511-7
11706047
Science. 2002 Feb 8;295(5557):1083-6
11834838