Comparative dynamics of retrograde actin flow and focal adhesions: formation of nascent adhesions triggers transition from fast to slow flow
Open accessAbstract
Dynamic actin network at the leading edge of the cell is linked to the extracellular matrix through focal adhesions (FAs), and at the same time it undergoes retrograde flow with different dynamics in two distinct zones: the lamellipodium (peripheral zone of fast flow), and the lamellum (zone of slow flow located between the lamellipodium and the cell body). Cell migration involves expansion of both the lamellipodium and the lamellum, as well as formation of new FAs, but it is largely unknown how the position of the boundary between the two flow zones is defined, and how FAs and actin flow mutually influence each other. We investigated dynamic relationship between focal adhesions and the boundary between the two flow zones in spreading cells. Nascent FAs first appeared in the lamellipodium. Within seconds after the formation of new FAs, the rate of actin flow decreased locally, and the lamellipodium/lamellum boundary advanced towards the new FAs. Blocking fast actin flow with cytochalasin D resulted in rapid dissolution of nascent FAs. In the absence of FAs (spreading on poly-L-lysine-coated surfaces) retrograde flow was uniform and the velocity transition was not observed. We conclude that formation of FAs depends on actin dynamics, and in its turn, affects the dynamics of actin flow by triggering transition from fast to slow flow. Extension of the cell edge thus proceeds through a cycle of lamellipodium protrusion, formation of new FAs, advance of the lamellum, and protrusion of the lamellipodium from the new base.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Arp2/3‐dependent branched actin has a specific role in counterbalancing microtubule‐induced contractile tension, potentially through its coupling to nascent adhesions and the substrate.
“Instead, these results point to a specific role for Arp2/3‐dependent branched actin in counterbalancing microtubule‐induced contractile tension, potentially through its coupling to nascent adhesions and the substrate [38, 39]”
From Paclitaxel induces <scp>NM2</scp> ‐dependent cellular contraction through <scp>GEF</scp> ‐ <scp>H1</scp> dissociation from microtubules and <scp>RhoA</scp> / <scp>ROCK</scp> activation in cancer cells (2026) · cites this paper as [38]
The Discussion (page unavailable in our copy) links lamellipodial actin flow to nascent adhesions and discusses a possible Arp2/3–vinculin connection to adhesion. It does not say that branched actin counterbalances microtubule-induced contractile tension; that part of the attributed claim is unsupported by this source. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 54
- [1]Ridley AJ Schwartz MA Burridge K Firtel RA Ginsberg MH 2003 Cell migration: integrating signals from front to back. Science 302 1704 1709 14657486
- [2]Mogilner A Oster G 2003 Polymer motors: pushing out the front and pulling up the back. Curr Biol 13 R721 733 13678614
- [3]Geiger B Bershadsky A Pankov R Yamada KM 2001 Transmembrane extracellular matrix–cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2 793 805 11715046
- [4]Kaverina I Krylyshkina O Small JV 2002 Regulation of substrate adhesion dynamics during cell motility. Int J Biochem Cell Biol 34 746 761 11950592
- [5]Webb DJ Brown CM Horwitz AF 2003 Illuminating adhesion complexes in migrating cells: moving toward a bright future. Curr Opin Cell Biol. 15 614 620 14519397
- [6]Sastry SK Burridge K 2000 Focal adhesions: a nexus for intracellular signaling and cytoskeletal dynamics. Exp Cell Res 261 25 36 11082272
- [7]Harris AK 1994 Locomotion of tissue culture cells considered in relation to ameboid locomotion. Int Rev Cytology 150 35 68 8169081
- [8]Cramer LP 1997 Molecular mechanism of actin-dependent retograde flow in lamellipodia of motile cells. Front Biosci 2 d260 270 9206973
- [9]Suter DM Forscher P 2000 Substrate-cytoskeletal coupling as a mechanism for the regulation of growth cone motility and guidance. J Neurobiol 44 97 113 10934315
- [10]Henson JH Svitkina TM Burns AR Hughes HE MacPartland KJ 1999 Two components of actin-based retrograde flow in sea urchin coelomocytes. Mol Biol Cell 10 4075 4090 10588644 PMC25744
- [11]Smilenov LB Mikhailov A Pelham RJ Marcantonio EE Gundersen GG 1999 Focal adhesion motility revealed in stationary fibroblasts. Science 286 1172 1174 10550057
- [12]Zamir E Katz M Posen Y Erez N Yamada KM 2000 Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts. Nat Cell Biol 2 191 196 10783236
- [13]Anderson KI Cross R 2000 Contact dynamics during keratocyte motility. Curr Biol 10 253 260 10712904
- [14]Small JV Geiger B Kaverina I Bershadsky A 2002 How do microtubules guide migrating cells? Nat Rev Mol Cell Biol. 3 957 64 12461561
- [15]Mitchison T Kirschner M 1988 Cytoskeletal dynamics and nerve growth. Neuron 1 761 772 3078414
- [16]Jay DG 2000 The clutch hypothesis revisited: ascribing the roles of actin-associated proteins in filopodial protrusion in the nerve growth cone. J Neurobiol 44 114 125 10934316
- [17]Jurado C Haserick JR Lee J 2005 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 15548591 PMC545886
- [18]Theriot JA Mitchison TJ 1992 Comparison of actin and cell surface dynamics in motile fibroblasts. J Cell Biol 119 367 377 1400580 PMC2289659
- [19]Hu K Ji L Applegate KT Danuser G Waterman-Storer CM 2007 Differential transmission of actin motion within focal adhesions. Science 315 111 115 17204653
- [20]Brown CM Hebert B Kolin DL Zareno J Whitmore L 2006 Probing the integrin-actin linkage using high-resolution protein velocity mapping. J Cell Sci 119 5204 5214 17158922
- [21]Salmon WC Adams MC Waterman-Storer CM 2002 Dual-wavelength fluorescent speckle microscopy reveals coupling of microtubule and actin movements in migrating cells. J Cell Biol 158 31 37 12105180 PMC2173033
- [22]Ponti A Machace M Gupton SL Waterman-Storer CM Danuser G 2004 Two distinct actin networks drive the protrusion of migrating cells. Science 305 1782 1786 15375270
- [23]Small JV Stradal T Vignal E Rottner K 2002 The lamellipodium: where motility begins. Trends Cell Biol 12 112 120 11859023
- [24]Gupton SL Anderson KL Kole TP Fischer RS Ponti A 2005 Cell migration without a lamellipodium: translation of actin dynamics into cell movement mediated by tropomyosin. J Cell Biol. 168 619 631 15716379 PMC2171771
- [25]Hotulainen P Lappalainen P 2006 Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J Cell Biol 173 383 394 16651381 PMC2063839
- [26]Giannone G Dubin-Thaler BJ Dobereiner HG Kieffer N Bresnick AR 2004 Periodic lamellipodial contractions correlate with rearward actin waves. Cell 116 431 443 15016377
- [27]Giannone G Dubin-Thaler BJ Rossier O Cai Y Chaga O 2007 Lamellipodial actin mechanically links myosin activity with adhesion-site formation. Cell 128 561 575 17289574 PMC5219974
- [28]Verkhovsky AB Chaga OY Schaub S Svitkina TM Meister JJ 2003 Orientational order of the lamellipodial actin network as demonstrated in living motile cells. Mol Biol Cell 14 4667 4675 13679520 PMC266781
- [29]Vallotton P Danuser G Bohnet S Meister JJ Verkhovsky AB 2005 Tracking retrograde flow in keratocytes: news from the front. Mol Biol Cell 16 1223 1231 15635099 PMC551487
- [30]Uehata M Ishizaki T Satoh H Ono T Kawahara T 1997 Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389 990 994 9353125
- [31]Volberg T Geiger B Citi S Bershadsky AD 1994 Effect of protein kinase inhibitor H-7 on the contractility, integrity, and membrane anchorage of the microfilament system. Cell Motil. Cytoskeleton 29 321 238 7859295
- [32]Rinnerthaler G Geiger B Small JV 1988 Contact formation during fibroblast locomotion: involvement of membrane ruffles and microtubules. J Cell Biol 106 747 760 3126193 PMC2115107
- [33]Endlich N Otey CA Kriz W Endlich K 2007 Movement of stress fibers away from focal adhesions identifies focal adhesions as sites of stress fiber assembly in stationary cells. Cell Motil Cytoskeleton 64 966 76 17868136
- [34]Verkhovsky AB Svitkina TM Borisy GG 1995 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 7490299 PMC2200006
- [35]Hotchin NA Hall A 1995 The assembly of integrin adhesion complexes requires both extracellular matrix and intracellular rho/rac GTPases. J Cell Biol 131 1857 1865 8557752 PMC2120648
- [36]Rottner K Hall A Small JV 1999 Interplay between Rac and Rho in the control of substrate contact dynamics. Curr Biol 9 640 648 10375527
- [37]Chrzanowska-Wodnicka M Burridge K 1996 Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J Cell Biol 133 1403 1415 8682874 PMC2120895
- [38]Zicha D Dobbie IM Holt MR Monypenny J Soong DY 2003 Rapid actin transport during cell protrusion. Science 300 142 145 12677069
- [39]Lee J Ishihara A Jacobson K 1993 The fish epidermal keratocyte as a model system for the study of cell locomotion. Symp Soc Exp Bio. 47 73 89 8165580
- [40]Suter DM Errante LD Belotserkovsky V Forscher P 1998 The Ig superfamily cell adhesion molecule, apCAM, mediates growth cone steering by substrate-cytoskeletal coupling. J Cell Biol 141 227 240 9531561 PMC2132711
- [41]Iwasa JH Mullins RD 2007 Spatial and temporal relationships between actin-filament nucleation, capping, and disassembly. Curr Biol 17 395 406 17331727 PMC3077992
- [42]Zigmond SH Evangelista M Boone C Yang C Dar AC 2003 Formin leaky cap allows elongation in the presence of tight capping proteins. Curr Biol 13 1820 1823 14561409
- [43]Goode BL Eck MJ 2007 Mechanism and function of formins in the control of actin assembly. Annu Rev Biochem 76 593 627 17373907
- [44]DeMali KA Barlow CA Burridge K 2002 Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion. J Cell Biol 159 881 891 12473693 PMC2173392
- [45]Riveline D Zamir E Balaban NQ Schwarz US Ishizaki T 2001 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 11402062 PMC2192034
- [46]Bershadsky AD Balaban NQ Geiger B 2003 Adhesion-dependent cell mechanosensitivity. Annu. Rev. Cell Dev Biol 19 677 695 14570586
- [47]Tamada M Sheetz MP Sawada Y 2004 Activation of a signaling cascade by cytoskeleton stretch. Dev Cell 7 709 718 15525532
- [48]Nicolas A Geiger B Safran SA 2004 Cell mechanosensitivity controls the anisotropy of focal adhesions. Proc Natl Acad Sci USA 101 12520 12525 15314229 PMC515090
- [49]Bruinsma R 2005 Theory of force regulation by nascent adhesion sites. Biophys J 89 87 94 15849245 PMC1366582
- [50]Beningo KA Dembo M Kaverina I Small JV Wang YL 2001 Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J Cell Biol 153 881 888 11352946 PMC2192381
- [51]Verkhovsky AB Svitkina TM Borisy GG 1997 Polarity sorting of actin filaments in cytochalasin-treated fibroblasts. J. Cell Sci 110 1693 1704 9264457
- [52]Choidas A Jungbluth A Sechi A Murphy J Ullrich A 1998 The suitability and application of a GFP-actin fusion protein for long-term imaging of the organization and dynamics of the cytoskeleton in mammalian cells. Eur J Cell Biol 77 81 90 9840457
- [53]Ballestrem C Wehrle-Haller B Imhof BA 1998 Actin dynamics in living mammalian cells. J Cell Sci 111 1649 1658 9601095
- [54]Morgenstern JP Land H 1990 Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line. Nucleic Acids Res 18 3587 3596 2194165 PMC331014
Cited by
Sorted by citations
Asensio‐Juárez, G., Pérez‐Díaz, R., Ramos‐Solano, H., Garrido‐Casado, M., Talayero, V. C., & Vicente‐Manzanares, M. (2026) · Molecular Oncology · doi:10.1002/1878-0261.70333
- Authors
- Alexandrova, A. Y., Arnold, K., Schaub, S., Vasiliev, J. M., Meister, J.-J., Bershadsky, A. D., & Verkhovsky, A. B.
- Affiliations
- Lomonosov Moscow State University (RU)
- Weizmann Institute of Science (IL)
- Centre National de la Recherche Scientifique (FR)
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Bershadsky, Alexander D.
- Verkhovsky, Alexander B.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-09-18
- Volume
- 3
- Issue
- 9
- Pages
- e3234
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2535565
- OpenAlex
- W2146667247
- Cited by
- 275
- References
- 0
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 8 · 2023: 14 · 2022: 12 · 2021: 7 · 2020: 20 · 2019: 13 · 2018: 15 · 2017: 14 · 2016: 17 · 2015: 20 · 2014: 24 · 2013: 22 · 2012: 18
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- actin retrograde flow, focal adhesions, nascent adhesions, lamellipodia, cell migration, cell spreading, actin dynamics, cytochalasin D, extracellular matrix adhesion
- MeSH terms
- Actins, Animals, Cell Movement, Cytoskeleton, Extracellular Matrix, Melanoma, Experimental, Actin Cytoskeleton, Microscopy, Microscopy, Phase-Contrast, Polylysine, Cytochalasin D, 3T3 Cells, Focal Adhesions, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review