Integration of actin dynamics and cell adhesion by a three-dimensional, mechanosensitive molecular clutch
Open accessAbstract
During cell migration, the forces generated in the actin cytoskeleton are transmitted across transmembrane receptors to the extracellular matrix or other cells through a series of mechanosensitive, regulable protein-protein interactions termed the molecular clutch. In integrin-based focal adhesions, the proteins forming this linkage are organized into a conserved three-dimensional nano-architecture. Here we discuss how the physical interactions between the actin cytoskeleton and focal-adhesion-associated molecules mediate force transmission from the molecular clutch to the extracellular matrix.
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Tensile force generated by polarized F-actin polymerization allows for integrin activation and focal adhesion maturation, both of which are necessary for cellular adhesion and migration through extracellular matrices.
“Tensile force generated by polarized F-actin polymerization allows for integrin activation and focal adhesion maturation, both of which are necessary for cellular adhesion and migration through extracellular matrices (Fig. 1b) [18, 19].”
From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [18]
In “The actin cytoskeleton is a master regulator of FAs” (page not given), the paper links actin flow to local integrin activation and says focal-adhesion maturation requires tension. It does not establish that polarized F-actin polymerization is the sole source of that tension: it also names myosin contractility and extracellular pulling. Its discussion of migration describes other mechanisms, so the claim that integrin activation and focal-adhesion maturation are necessary for migration through extracellular matrices is too broad. (LLM, conf=0.87)
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Mechanisms that regulate adaptor binding to β-integrin cytoplasmic tails
Legate, K. R., & Fässler, R. (2009) · Journal of Cell Science · doi:10.1242/jcs.041624 · Cited by 370 · see citing works
Structural Basis for Activation and Inhibition of Class I Phosphoinositide 3-Kinases
Vadas, O., Burke, J. E., Zhang, X., Berndt, A., & Williams, R. L. (2011) · Science Signaling · doi:10.1126/scisignal.2002165 · Cited by 299 · see citing works
Mechanotransduction In Vivo by Repeated Talin Stretch-Relaxation Events Depends upon Vinculin
Margadant, F., Chew, L. L., Hu, X., Yu, H., Bate, N., Zhang, X., & Sheetz, M. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001223 · Cited by 215 · see citing works
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Research works printed but not linked: 145
- [1]Friedl P Prespecification and plasticity: shifting mechanisms of cell migration. Curr. Opin. Cell Biol 16, 14– 23 (2004). 15037300
- [2]Paluch EK & Raz E The role and regulation of blebs in cell migration. Curr. Opin. Cell Biol 25, 582– 590 (2013). 23786923 PMC3989058
- [3]Stroka KM Water permeation drives tumor cell migration in confined microenvironments. Cell 157, 611– 623 (2014). 24726433 PMC4365996
- [4]Renkawitz J Adaptive force transmission in amoeboid cell migration. Nat. Cell Biol 11, 1438– 1443 (2009). 19915557
- [5]Petrie RJ, Koo H & Yamada KM Generation of compartmentalized pressure by a nuclear piston governs cell motility in a 3D matrix. Science 345, 1062– 1065 (2014). 25170155 PMC5248932
- [6]Pollard TD & Cooper JA Actin, a central player in cell shape and movement. Science 326, 1208– 1212 (2009). 19965462 PMC3677050
- [7]Liu Y-J Confinement and low adhesion induce fast amoeboid migration of slow mesenchymal cells. Cell 160, 659– 672 (2015). 25679760
- [8]Ruprecht V Cortical contractility triggers a stochastic switch to fast amoeboid cell motility. Cell 160, 673– 685 (2015). 25679761 PMC4328143
- [9]Petrie RJ, Doyle AD & Yamada KM Random versus directionally persistent cell migration. Nat. Rev. Mol. Cell Biol 10, 538– 549 (2009). 19603038 PMC2752299
- [10]Wang YL Exchange of actin subunits at the leading edge of living fibroblasts: possible role of treadmilling. J. Cell Biol 101, 597– 602 (1985). 4040521 PMC2113673
- [11]Theriot JA & Mitchison TJ Actin microfilament dynamics in locomoting cells. Nature 352, 126– 131 (1991). 2067574
- [12]Mogilner A & Oster G Cell motility driven by actin polymerization. Biophys. J 71, 3030– 3045 (1996). 8968574 PMC1233792
- [13]Lin CH & Forscher P Growth cone advance is inversely proportional to retrograde F-actin flow. Neuron 14, 763– 771 (1995). 7536426
- [14]Mitchison T & Kirschner M Cytoskeletal dynamics and nerve growth. Neuron 1, 761– 772 (1988). 3078414
- [15]Marjoram RJ, Lessey EC & Burridge K Regulation of RhoA activity by adhesion molecules and mechanotransduction. Curr. Mol. Med 14, 199– 208 (2014). 24467208 PMC3929014
- [16]Rose DM, Alon R & Ginsberg MH Integrin modulation and signaling in leukocyte adhesion and migration. Immunol. Rev 218, 126– 134 (2007). 17624949
- [17]Dunn GA & Jones GE Cell motility under the microscope: Vorsprung durch Technik. Nat. Rev. Mol. Cell Biol 5, 667– 672 (2004). 15366710
- [18]Abercrombie M The bases of the locomotory behaviour of fibroblasts. Exp. Cell Res 8, 188– 198 (1961). 13681019
- [19]Abercrombie M, Heaysman JEM & Pegrum SM The locomotion of fibroblasts in culture: I. Movements of the leading edge. Exp. Cell Res 59, 393– 398 (1970). 4907703
- [20]Abercrombie M, Heaysman JEM & Pegrum SM The locomotion of fibroblasts in culture: III. Movements of particles on the dorsal surface of the leading lamella. Exp. Cell Res 62, 389– 398 (1970). 5531377
- [21]Harris A & Dunn G Centripetal transport of attached particles on both surfaces of moving fibroblasts. Exp. Cell Res 73, 519– 523 (1972). 4559927
- [22]Harris AK Cell surface movements related to cell locomotion. Ciba Found. Symp 14, 3– 26 (1973). 4591637
- [23]Abercrombie M, Heaysman JEM & Pegrum SM The locomotion of fibroblasts in culture: IV. Electron microscopy of the leading lamella. Exp. Cell Res 67, 359– 367 (1971). 5097522
- [24]Small JV, Isenberg G & Celis JE Polarity of actin at the leading edge of cultured cells. Nature 272, 638– 639 (1978). 565473
- [25]Forscher P Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone. J. Cell Biol. 107, 1505– 1516 (1988). 3170637 PMC2115246
- [26]Lee J, Ishihara A, Theriot JA & Jacobson K Principles of locomotion for simple-shaped cells. Nature 362, 167– 171 (1993). 8450887
- [27]Henson JH Two components of actin-based retrograde flow in sea urchin coelomocytes. Mol. Biol. Cell 10, 4075– 4090 (1999). 10588644 PMC25744
- [28]Ponti A, Machacek M, Gupton SL, Waterman-Storer CM & Danuser G Two distinct actin networks drive the protrusion of migrating cells. Science 305, 1782– 1786 (2004). 15375270
- [29]Cramer LP Molecular mechanism of actin-dependent retrograde flow in lamellipodia of motile cells. Front. Biosci 2, 260– 70 (1997). 9206973
- [30]Cortese JD, Schwab B, Frieden C & Elson EL Actin polymerization induces a shape change in actin-containing vesicles. Proc. Natl Acad. Sci. USA 86, 5773– 5777 (1989). 2548187 PMC297712
- [31]Alberts JB & Odell GM In silico reconstitution of Listeria propulsion exhibits nano-saltation. PLoS Biol. 2, e412 (2004). 15562315 PMC532387
- [32]Iwasa JH & Mullins RD Spatial and temporal relationships between actin-filament nucleation, capping, and disassembly. Curr. Biol 17, 395– 406 (2007). 17331727 PMC3077992
- [33]Hotulainen P & Lappalainen P Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J. Cell Biol 173, 383– 394 (2006). 16651381 PMC2063839
- [34]Small JVV, Rottner K, Kaverina I & Anderson KII Assembling an actin cytoskeleton for cell attachment and movement. Biochim. Biophys. Acta 1404, 271– 281 (1998). 9739149
- [35]Kovac B, Teo JL, Mäkelä TP & Vallenius T Assembly of non-contractile dorsal stress fibers requires α-actinin−1 and Rac1 in migrating and spreading cells. J. Cell Sci 126, 263– 73 (2013). 23132927
- [36]Verkhovsky AB, Svitkina TM & Borisy GG Myosin II filament assemblies in the active lamella of fibroblasts: their morphogenesis and role in the formation of actin filament bundles. J. Cell Biol 131, 989– 1002 (1995). 7490299 PMC2200006
- [37]Wilson CA Myosin II contributes to cell-scale actin network treadmilling through network disassembly. Nature 465, 373– 377 (2010). 20485438 PMC3662466
- [38]Waterman-Storer CM & Salmon ED Actomyosin-based retrograde flow of microtubules in the lamella of migrating epithelial cells influences microtubule dynamic instability and turnover and is associated with microtubule breakage and treadmilling. J. Cell Biol 139, 417– 434 (1997). 9334345 PMC2139796
- [39]Gardel ML Traction stress in focal adhesions correlates biphasically with actin retrograde flow speed. J. Cell Biol 183, 999– 1005 (2008). 19075110 PMC2600750
- [40]Medeiros NA, Burnette DT & Forscher P Myosin II functions in actin-bundle turnover in neuronal growth cones. Nat. Cell Biol 8, 215– 226 (2006). 16501565
- [41]Jurado C, Haserick JR & Lee J Slipping or gripping? Fluorescent speckle microscopy in fish keratocytes reveals two different mechanisms for generating a retrograde flow of actin. Mol. Biol. Cell 16, 507– 518 (2005). 15548591 PMC545886
- [42]Vallotton P, Danuser G, Bohnet S, Meister J-J & Verkhovsky AB Tracking retrograde flow in keratocytes: news from the front. Mol. Biol. Cell 16, 1223– 1231 (2005). 15635099 PMC551487
- [43]Del Alamo JC Spatio-temporal analysis of eukaryotic cell motility by improved force cytometry. Proc. Natl Acad. Sci. USA 104, 13343– 13348 (2007). 17684097 PMC1940228
- [44]Hynes RO & Destree AT Relationships between fibronectin (LETS protein) and actin. Cell 15, 875– 886 (1978). 365353
- [45]Singer II The fibronexus: a transmembrane association of fibronectin-containing fibers and bundles of 5 nm microfilaments in hamster and human fibroblasts. Cell 16, 675– 685 (1979). 222466
- [46]Singer II Association of fibronectin and vinculin with focal contacts and stress fibers in stationary hamster fibroblasts. J. Cell Biol. 92, 398– 408 (1982). 6801062 PMC2112091
- [47]Tamkun JW Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Cell 46, 271– 282 (1986). 3487386
- [48]Hynes RO Integrins: bidirectional, allosteric signaling machines. Cell 110, 673– 687 (2002). 12297042
- [49]Takagi J, Erickson HP & Springer TA C-terminal opening mimics “inside-out” activation of integrin α5β1. Nat. Struct. Biol 8, 412– 416 (2001). 11323715
- [50]Takagi J, Petre BM, Walz T & Springer TA Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell 110, 599– 611 (2002). 12230977
- [51]Calderwood DA The talin head domain binds to integrin subunit cytoplasmic tails and regulates integrin activation. J. Biol. Chem 274, 28071– 28074 (1999). 10497155
- [52]Otey CA, Pavalko FM & Burridge K An interaction between α-actinin and the β1 integrin subunit in vitro. J. Cell Biol 111, 721– 729 (1990). 2116421 PMC2116186
- [53]Harburger DS, Bouaouina M & Calderwood DA Kindlin−1 and −2 directly bind the C-terminal region of β integrin cytoplasmic tails and exert integrin-specific activation effects. J. Biol. Chem 284, 11485– 11497 (2009). 19240021 PMC2670154
- [54]Calderwood DA Integrin β cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling. Proc. Natl Acad. Sci. USA 100, 2272– 2277 (2003). 12606711 PMC151330
- [56]Morse EM, Brahme NN & Calderwood DA Integrin cytoplasmic tail interactions. Biochemistry 53, 810– 820 (2014). 24467163 PMC3985435
- [57]Zaidel-Bar R, Itzkovitz S, Ma’ayan A, Iyengar R & Geiger B Functional atlas of the integrin adhesome. Nat. Cell Biol 9, 858– 867 (2007). 17671451 PMC2735470
- [58]Kuo J-CC, Han X, Hsiao C-TT, Yates JR Iii& Waterman CM Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nat. Cell Biol 13, 383– 393 (2011). 21423176 PMC3279191
- [59]Byron A, Humphries JD, Bass MD, Knight D & Humphries MJ Proteomic analysis of integrin adhesion complexes. Sci. Signal 4, 2 (2011). 21467297
- [60]Schiller HB, Friedel CC, Boulegue C & Fässler R Quantitative proteomics of the integrin adhesome show a myosin II-dependent recruitment of LIM domain proteins. EMBO Rep. 12, 259– 266 (2011). 21311561 PMC3059911
- [61]Zaidel-Bar R, Ballestrem C, Kam Z & Geiger B Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells. J. Cell Sci 116, 4605– 4613 (2003). 14576354
- [62]Choi CK Actin and α-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner. Nat. Cell Biol 10, 1039– 1050 (2008). 19160484 PMC2827253
- [63]Lawson C FAK promotes recruitment of talin to nascent adhesions to control cell motility. J. Cell Biol. 196, 223– 232 (2012). 22270917 PMC3265949
- [64]Oakes PW, Beckham Y, Stricker J & Gardel ML Tension is required but not sufficient for focal adhesion maturation without a stress fiber template. J. Cell Biol 196, 363– 374 (2012). 22291038 PMC3275371
- [65]Shroff H Dual-color superresolution imaging of genetically expressed probes within individual adhesion complexes. Proc. Natl Acad. Sci. USA 104, 20308– 20313 (2007). 18077327 PMC2154427
- [66]Shtengel G Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure. Proc. Natl Acad. Sci. USA 106, 3125– 3130 (2009). 19202073 PMC2637278
- [67]Kanchanawong P Nanoscale architecture of integrin-based cell adhesions. Nature 468, 580– 584 (2010). 21107430 PMC3046339
- [68]Paszek MJ Scanning angle interference microscopy reveals cell dynamics at the nanoscale. Nat. Methods 9, 825– 827 (2012). 22751201 PMC3454456
- [69]Case LB Molecular mechanism of vinculin activation and nanoscale spatial organization in focal adhesions. Nat. Cell Biol 17, 880– 892 (2015). 26053221 PMC4490039
- [70]Critchley DR Biochemical and structural properties of the integrin-associated cytoskeletal protein talin. Annu. Rev. Biophys 38, 235– 254 (2009). 19416068
- [71]Horwitz A, Duggan K, Buck C, Beckerle MC & Burridge K Interaction of plasma membrane fibronectin receptor with talin — a transmembrane linkage. Nature 320, 531– 533 (1986). 2938015
- [72]Goldmann WH Examining F-actin interaction with intact talin and talin head and tail fragment using static and dynamic light scattering. Eur. J. Biochem 250, 447– 450 (1997). 9428697
- [73]Wolfenson H A role for the juxtamembrane cytoplasm in the molecular dynamics of focal adhesions. PLoS One 4, e4304 (2009). 19172999 PMC2627934
- [74]Zamir E Molecular diversity of cell-matrix adhesions. J. Cell Sci 112, 1655– 1669 (1999). 10318759
- [75]Zaidel-Bar R, Milo R, Kam Z & Geiger B A paxillin tyrosine phosphorylation switch regulates the assembly and form of cell-matrix adhesions. J. Cell Sci 120, 137– 148 (2007). 17164291
- [77]Shibata ACE Archipelago architecture of the focal adhesion: membrane molecules freely enter and exit from the focal adhesion zone. Cytoskeleton 69, 380– 392 (2012). 22488960
- [78]Rossier O Integrins β1 and β3 exhibit distinct dynamic nanoscale organizations inside focal adhesions. Nat. Cell Biol 14, 1057– 1067 (2012). 23023225
- [79]Von Wichert G, Haimovich B, Feng G-S & Sheetz MP Force-dependent integrincytoskeleton linkage formation requires downregulation of focal complex dynamics by Shp2. EMBO J. 22, 5023– 5035 (2003). 14517241 PMC204475
- [80]Lele TP, Thodeti CK, Pendse J & Ingber DE Investigating complexity of protein-protein interactions in focal adhesions. Biochem. Biophys. Res. Commun 369, 929– 934 (2008). 18331831 PMC2730744
- [81]Lavelin I Differential effect of actomyosin relaxation on the dynamic properties of focal adhesion proteins. PLoS One 8, e73549 (2013). 24039980 PMC3767655
- [82]Bachir AI Integrin-associated complexes form hierarchically with variable stoichiometry in ascent adhesions. Curr. Biol 24, 1845– 1853 (2014). 25088556 PMC4138543
- [83]Hoffmann J-E, Fermin Y, Stricker RL, Ickstadt K & Zamir E Symmetric exchange of multi-protein building blocks between stationary focal adhesions and the cytosol. eLife 3, e02257 (2014). 24894463 PMC4040925
- [84]Shemesh T, Verkhovsky AB, Svitkina TM, Bershadsky AD & Kozlov MM Role of focal adhesions and mechanical stresses in the formation and progression of the lamellipodium-lamellum interface [corrected]. Biophys. J 97, 1254– 1264 (2009). 19720013 PMC2749772
- [85]Balaban NQ Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat. Cell Biol. 3, 466– 472 (2001). 11331874
- [86]Alexandrova AY Comparative dynamics of retrograde actin flow and focal adhesions: formation of nascent adhesions triggers transition from fast to slow flow. PLoS One 3, e3234 (2008). 18800171 PMC2535565
- [87]Gupton SL & Waterman-Storer CM Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration. Cell 125, 1361– 1374 (2006). 16814721
- [88]Chrzanowska-Wodnicka M & Burridge K Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J. Cell Biol 133, 1403– 1415 (1996). 8682874 PMC2120895
- [89]Webb DJ FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat. Cell Biol 6, 154– 161 (2004). 14743221
- [90]Zhu J Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol. Cell 32, 849– 861 (2008). 19111664 PMC2758073
- [91]Tanentzapf G & Brown NH An interaction between integrin and the talin FERM domain mediates integrin activation but not linkage to the cytoskeleton. Nat. Cell Biol 8, 601– 606 (2006). 16648844
- [92]O’Toole TE Integrin cytoplasmic domains mediate inside-out signal transduction. J. Cell Biol 124, 1047– 1059 (1994). 7510712 PMC2119979
- [93]Anthis NJ The structure of an integrin/talin complex reveals the basis of inside-out signal transduction. EMBO J. 28, 3623– 3632 (2009). 19798053 PMC2782098
- [94]Huttenlocher A, Ginsberg MH & Horwitz AF Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity. J Cell Biol 134, 1551– 1562 (1996). 8830782 PMC2121008
- [95]Chigaev A, Buranda T, Dwyer DC, Prossnitz ER & Sklar LA FRET detection of cellular α4-integrin conformational activation. Biophys. J 85, 3951– 3962 (2003). 14645084 PMC1303696
- [96]Kim M, Carman CV & Springer TA Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 301, 1720– 1725 (2003). 14500982
- [97]Wu C Arp2/3 is critical for lamellipodia and response to extracellular matrix cues but is dispensable for chemotaxis. Cell 148, 973– 987 (2012). 22385962 PMC3707508
- [98]Beckham Y Arp2/3 inhibition induces amoeboid-like protrusions in MCF10A epithelial cells by reduced cytoskeletal-membrane coupling and focal adhesion assembly. PLoS One 9, e100943 (2014). 24967897 PMC4072770
- [99]DeMali KA, Barlow CA & Burridge K Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion. J. Cell Biol 159, 881– 891 (2002). 12473693 PMC2173392
- [100]Serrels B Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex. Nat. Cell Biol 9, 1046– 1056 (2007). 17721515
- [101]Laukaitis CM, Webb DJ, Donais K & Horwitz AF Differential dynamics of α5 integrin, paxillin, and α-actinin during formation and disassembly of adhesions in migrating cells. J. Cell Biol 153, 1427– 1440 (2001). 11425873 PMC2150721
- [102]Vicente-Manzanares M, Zareno J, Whitmore L, Choi CK & Horwitz AF Regulation of protrusion, adhesion dynamics, and polarity by myosins IIA and IIB in migrating cells. J. Cell Biol 176, 573– 580 (2007). 17312025 PMC2064016
- [103]Thievessen I Vinculin-actin interaction couples actin retrograde flow to focal adhesions, but is dispensable for focal adhesion growth. J. Cell Biol 202, 163– 177 (2013). 23836933 PMC3704983
- [104]Riveline D Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J. Cell Biol 153, 1175– 1186 (2001). 11402062 PMC2192034
- [105]Galbraith CG, Yamada KM & Sheetz MP The relationship between force and focal complex development. J. Cell Biol 159, 695– 705 (2002). 12446745 PMC2173098
- [106]Helfman DM Caldesmon inhibits nonmuscle cell contractility and interferes with the formation of focal adhesions. Mol. Biol. Cell 10, 3097– 3112 (1999). 10512853 PMC25564
- [107]Shemesh T, Geiger B, Bershadsky AD & Kozlov MM Focal adhesions as mechanosensors: a physical mechanism. Proc. Natl Acad. Sci. USA 102, 12383– 12388 (2005). 16113084 PMC1194898
- [108]Wang N, Butler JP & Ingber DE Mechanotransduction across the cell surface and through the cytoskeleton. Science 260, 1124– 1127 (1993). 7684161
- [109]Choquet D, Felsenfeld DP & Sheetz MP Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages. Cell 88, 39– 48 (1997). 9019403
- [110]Gupton SL, Eisenmann K, Alberts AS & Waterman-Storer CM mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration. J. Cell Sci 120, 3475– 3587 (2007). 17855386
- [111]Plotnikov SV, Pasapera AM, Sabass B & Waterman CM Force fluctuations within focal adhesions mediate ECM-rigidity sensing to guide directed cell migration. Cell 151, 1513– 1527 (2012). 23260139 PMC3821979
- [112]Grashoff C Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466, 263– 266 (2010). 20613844 PMC2901888
- [113]Liu Y, Yehl K, Narui Y & Salaita K Tension sensing nanoparticles for mechano-imaging at the living/nonliving interface. J. Am. Chem. Soc 135, 5320– 5323 (2013). 23495954 PMC3630457
- [114]Morimatsu M, Mekhdjian AH, Adhikari AS & Dunn AR Molecular tension sensors report forces generated by single integrin molecules in living cells. Nano Lett. 13, 3985– 3989 (2013). 23859772 PMC3815579
- [115]Wang X & Ha T Defining single molecular forces required to activate integrin and notch signaling. Science 340, 991– 994 (2013). 23704575 PMC3710701
- [116]Jurchenko C, Chang Y, Narui Y, Zhang Y & Salaita KS Integrin-generated forces lead to streptavidin-biotin unbinding in cellular adhesions. Biophys. J 106, 1436– 1446 (2014). 24703305 PMC3976516
- [117]Sawada Y Force sensing by mechanical extension of the Src family kinase substrate p130Cas. Cell 127, 1015– 1026 (2006). 17129785 PMC2746973
- [118]Kong F, García AJ, Mould AP, Humphries MJ & Zhu C Demonstration of catch bonds between an integrin and its ligand. J. Cell Biol 185, 1275– 1284 (2009). 19564406 PMC2712956
- [119]Jiang G, Giannone G, Critchley DR, Fukumoto E & Sheetz MP Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin. Nature 424, 334– 337 (2003). 12867986
- [120]Del Rio A Stretching single talin rod molecules activates vinculin binding. Science 323, 638– 641 (2009). 19179532 PMC9339221
- [121]Yao M Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation. Sci. Rep 4, 4610 (2014). 24714394 PMC3980218
- [122]Kozlov MM & Bershadsky AD Processive capping by formin suggests a force-driven mechanism of actin polymerization. J. Cell Biol 167, 1011– 1017 (2004). 15596547 PMC2172604
- [123]Jégou A, Carlier M-F & Romet-Lemonne G Formin mDia1 senses and generates mechanical forces on actin filaments. Nat. Commun 4, 1883 (2013). 23695677
- [124]Hu K, Ji L, Applegate KT, Danuser G & Waterman-Storer CM Differential transmission of actin motion within focal adhesions. Science 315, 111– 115 (2007). 17204653
- [125]Sabass B, Gardel ML, Waterman CM & Schwarz US High resolution traction force microscopy based on experimental and computational advances. Biophys. J 94, 207– 220 (2008). 17827246 PMC2134850
- [126]Brown CM Probing the integrin-actin linkage using high-resolution protein velocity mapping. J. Cell Sci 119, 5204– 5214 (2006). 17158922
- [127]Chan CE & Odde DJ Traction dynamics of filopodia on compliant substrates. Science 322, 1687– 1691 (2008). 19074349
- [128]Shemesh T, Bershadsky AD & Kozlov MM Physical model for self-organization of actin cytoskeleton and adhesion complexes at the cell front. Biophys. J 102, 1746– 1756 (2012). 22768930 PMC3328692
- [129]Giannone G, Jiang G, Sutton DH, Critchley DR & Sheetz MP Talin1 is critical for force-dependent reinforcement of initial integrin-cytoskeleton bonds but not tyrosine kinase activation. J. Cell Biol 163, 409– 419 (2003). 14581461 PMC2173516
- [130]Zhang X Talin depletion reveals independence of initial cell spreading from integrin activation and traction. Nat. Cell Biol 10, 1062– 1068 (2008). 19160486 PMC2746969
- [131]Chen H, Choudhury DM & Craig SW Coincidence of actin filaments and talin is required to activate vinculin. J. Biol. Chem 281, 40389– 40398 (2006). 17074767
- [132]Dumbauld DW How vinculin regulates force transmission. Proc. Natl Acad. Sci. USA 110, 9788– 9793 (2013). 23716647 PMC3683711
- [133]Diez G, Auernheimer V, Fabry B & Goldmann WH Head/tail interaction of vinculin influences cell mechanical behavior. Biochem. Biophys. Res. Commun 406, 85– 88 (2011). 21295550
- [134]Roca-Cusachs P Integrin-dependent force transmission to the extracellular matrix by α-actinin triggers adhesion maturation. Proc. Natl Acad. Sci. USA 110, 1361– 1370 (2013). PMC3625291 23515331
- [135]Giannone G Periodic lamellipodial contractions correlate with rearward actin waves. Cell 116, 431– 443 (2004). 15016377
- [136]Vasquez CG, Tworoger M & Martin AC Dynamic myosin phosphorylation regulates contractile pulses and tissue integrity during epithelial morphogenesis. J. Cell Biol 206, 435– 450 (2014). 25092658 PMC4121972
- [137]Giannone G Lamellipodial actin mechanically links myosin activity with adhesion-site formation. Cell 128, 561– 575 (2007). 17289574 PMC5219974
- [138]Muller WA Mechanisms of leukocyte transendothelial migration. Annu. Rev. Pathol 6, 323– 344 (2011). 21073340 PMC3628537
- [139]Celli L, Ryckewaert J-J, Delachanal E & Duperray A Evidence of a functional role for interaction between ICAM−1 and nonmuscle α-actinins in leukocyte diapedesis. J. Immunol 177, 4113– 4121 (2006). 16951376
- [140]Martinelli R Release of cellular tension signals self-restorative ventral lamellipodia to heal barrier micro-wounds. J. Cell Biol 201, 449– 465 (2013). 23629967 PMC3639391
- [141]Dustin ML Cell adhesion molecules and actin cytoskeleton at immune synapses and kinapses. Curr. Opin. Cell Biol 19, 529– 533 (2007). 17923403 PMC2486492
- [142]Hauck CR, Agerer F, Muenzner P & Schmitter T Cellular adhesion molecules as targets for bacterial infection. Eur. J. Cell Biol 85, 235– 242 (2006). 16546567
- [143]Hamiaux C, van Eerde A, Parsot C, Broos J & Dijkstra BW Structural mimicry for vinculin activation by IpaA, a virulence factor of Shigella flexneri. EMBO Rep. 7, 794– 799 (2006). 16826238 PMC1525141
- [144]Leckband DE & de Rooij J Cadherin adhesion and mechanotransduction. Annu. Rev. Cell Dev. Biol 30, 291– 315 (2014). 25062360
- [145]Bard L A molecular clutch between the actin flow and N-cadherin adhesions drives growth cone migration. J. Neurosci 28, 5879– 5890 (2008). 18524892 PMC6670336
- [146]Kametani Y & Takeichi M Basal-to-apical cadherin flow at cell junctions. Nat. Cell Biol 9, 92– 98 (2007). 17159998
- [147]Locascio A & Nieto MA Cell movements during vertebrate development: integrated tissue behaviour versus individual cell migration. Curr. Opin. Genet. Dev 11, 464– 469 (2001). 11448634
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- Authors
- Case, L. B., & Waterman, C. M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Waterman, Clare M.
- Venue
- Nature Cell Biology
- Published
- 2015-06-29
- Volume
- 17
- Issue
- 8
- Pages
- 955-963
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC6300998
- OpenAlex
- W2211191608
- Cited by
- 520
- References
- 3
- Citations by year
- 2026: 30 · 2025: 48 · 2024: 43 · 2023: 56 · 2022: 58 · 2021: 47 · 2020: 55 · 2019: 41 · 2018: 46 · 2017: 57 · 2016: 32 · 2015: 7
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (Z01HL005105)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
- Keywords
- molecular clutch, actin cytoskeleton, cell adhesion, integrins, focal adhesions, force transmission, extracellular matrix, cell migration
- MeSH terms
- Actins, Animals, Cell Adhesion, Cell Movement, Humans, Actin Cytoskeleton, Pressure, Time Factors, Integrins, Extracellular Matrix Proteins, Focal Adhesions, Mechanotransduction, Cellular
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