title: Asymmetric friction of nonmotor MAPs can lead to their directional motion in active microtubule networks.
abstract: Diverse cellular processes require microtubules to be organized into distinct structures, such as asters or bundles. Within these dynamic motifs, microtubule-associated proteins (MAPs) are frequently under load, but how force modulates these proteins' function is poorly understood. Here, we combine optical trapping with TIRF-based microscopy to measure the force dependence of microtubule interaction for three nonmotor MAPs (NuMA, PRC1, and EB1) required for cell division. We find that frictional forces increase nonlinearly with MAP velocity across microtubules and depend on filament polarity, with NuMA's friction being lower when moving toward minus ends, EB1's lower toward plus ends, and PRC1's exhibiting no directional preference. Mathematical models predict, and experiments confirm, that MAPs with asymmetric friction can move directionally within actively moving microtubule pairs they crosslink. Our findings reveal how nonmotor MAPs can generate frictional resistance in dynamic cytoskeletal networks via micromechanical adaptations whose anisotropy may be optimized for MAP localization and function within cellular structures.
authors.affiliation: Laboratory of Chemistry and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Forth
authors.affiliation: Laboratory of Chemistry and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Kuo-Chiang
authors.initials: KC
authors.lastname: Hsia
authors.affiliation: Laboratory of Chemistry and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Shimamoto
authors.affiliation: Laboratory of Chemistry and Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: kapoor@rockefeller.edu.
authors.forename: Tarun M
authors.initials: TM
authors.lastname: Kapoor
mesh_terms: D034961:Antigens, Nuclear / Q000737:chemistry / Q000378:metabolism*; D001696:Biomechanical Phenomena; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D034521:Nuclear Matrix-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D052898:Optical Tweezers
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; C116662:PRC1 protein, human
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):492-7
references.pmid: 19126680
references.citation: J Biol Chem. 2003 Sep 19;278(38):36430-4
references.pmid: 12857735
references.citation: Curr Biol. 2006 Nov 7;16(21):2111-22
references.pmid: 17084695
references.citation: Curr Opin Cell Biol. 2011 Feb;23(1):94-101
references.pmid: 20817499
references.citation: Cell. 2010 Aug 6;142(3):420-32
references.pmid: 20691901
references.citation: Mol Cell. 2007 Sep 21;27(6):976-91
references.pmid: 17889670
references.citation: J Cell Biol. 2010 May 3;189(3):465-80
references.pmid: 20439998
references.citation: Nature. 2007 Dec 13;450(7172):1100-5
references.pmid: 18059460
references.citation: Mol Biol Cell. 2013 May;24(10):1559-73
references.pmid: 23515222
references.citation: Nat Cell Biol. 2007 Nov;9(11):1233-42
references.pmid: 17934454
references.citation: Cell. 1994 Jun 3;77(5):773-84
references.pmid: 8205624
references.citation: J Cell Sci. 2004 Dec 15;117(Pt 26):6391-400
references.pmid: 15561764
references.citation: PLoS Biol. 2009 Apr 21;7(4):e1000087
references.pmid: 19385717
references.citation: Mol Syst Biol. 2008;4:195
references.pmid: 18463619
references.citation: Cell. 2009 Jul 23;138(2):366-76
references.pmid: 19632184
references.citation: J Cell Biol. 2008 Aug 25;182(4):631-9
references.pmid: 18710922
references.citation: Cell. 2007 Jan 26;128(2):357-68
references.pmid: 17254972
references.citation: Cell. 2013 Jul 18;154(2):377-90
references.pmid: 23870126
references.citation: Curr Biol. 2009 Dec 15;19(23):R1089-94
references.pmid: 20064413
references.citation: Mol Biol Cell. 2011 Aug 15;22(16):2912-23
references.pmid: 21737692
references.citation: Cell. 1996 Nov 1;87(3):447-58
references.pmid: 8898198
references.citation: Nat Struct Mol Biol. 2009 Feb;16(2):124-9
references.pmid: 19136959
references.citation: PLoS One. 2009 Oct 23;4(10):e7585
references.pmid: 19851462
references.citation: Curr Biol. 2011 Jan 25;21(2):154-60
references.pmid: 21236672
references.citation: Curr Biol. 2012 Oct 9;22(19):1800-7
references.pmid: 22885064
references.citation: Cell. 2007 Nov 30;131(5):952-65
references.pmid: 18045537
references.citation: Phys Rev Lett. 1993 Sep 6;71(10):1477-1481
references.pmid: 10054418
references.citation: Cell. 2010 Aug 6;142(3):433-43
references.pmid: 20691902
references.citation: Nat Cell Biol. 2001 Jan;3(1):E17-21
references.pmid: 11146645
references.citation: Nat Cell Biol. 2011 Sep 04;13(10):1259-64
references.pmid: 21892183
references.citation: J Cell Biol. 2000 May 15;149(4):851-62
references.pmid: 10811826
references.citation: Cell. 2012 Apr 13;149(2):371-82
references.pmid: 22500803
references.citation: Nature. 2004 Feb 12;427(6975):649-52
references.pmid: 14961123
references.citation: Dev Cell. 2012 Nov 13;23(5):874-85
references.pmid: 23153484
references.citation: J Cell Biol. 2002 Jun 24;157(7):1175-86
references.pmid: 12082078
references.citation: Acc Chem Res. 2001 Jun;34(6):412-20
references.pmid: 11412078
references.citation: J Cell Biol. 1996 Oct;135(2):399-414
references.pmid: 8896597
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5741-5
references.pmid: 16585530
references.citation: J Cell Biol. 1992 Mar;116(6):1395-408
references.pmid: 1541636
references.citation: J Cell Sci. 2002 May 1;115(Pt 9):1815-24
references.pmid: 11956313
references.citation: J Cell Biol. 1995 Nov;131(3):693-708
references.pmid: 7593190
references.citation: J Cell Biol. 1997 Aug 11;138(3):615-28
references.pmid: 9245790
references.citation: Science. 2009 Aug 14;325(5942):870-3
references.pmid: 19679813
references.citation: Trends Biochem Sci. 2002 Oct;27(10):527-33
references.pmid: 12368089
references.citation: Nat Cell Biol. 2006 May;8(5):470-6
references.pmid: 16604065
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5977-81
references.pmid: 11959922