The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles
Open accessPublished version of a preprint
Abstract
To navigate through diverse tissues, migrating cells must balance persistent self-propelled motion with adaptive behaviors to circumvent obstacles. We identify a curvature-sensing mechanism underlying obstacle evasion in immune-like cells. Specifically, we propose that actin polymerization at the advancing edge of migrating cells is inhibited by the curvature-sensitive BAR domain protein Snx33 in regions with inward plasma membrane curvature. The genetic perturbation of this machinery reduces the cells’ capacity to evade obstructions combined with faster and more persistent cell migration in obstacle-free environments. Our results show how cells can read out their surface topography and utilize actin and plasma membrane biophysics to interpret their environment, allowing them to adaptively decide if they should move ahead or turn away. On the basis of our findings, we propose that the natural diversity of BAR domain proteins may allow cells to tune their curvature sensing machinery to match the shape characteristics in their environment.
Overview
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
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Protein complex prediction with AlphaFold-Multimer
Evans, R., O’Neill, M., Pritzel, A., Antropova, N., Senior, A., Green, T., Žídek, A., Bates, R., Blackwell, S., Yim, J., et al. (2021) · doi:10.1101/2021.10.04.463034 · Cited by 3,808
The actin cytoskeleton and actin-based motility
Svitkina, T. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a018267 · Cited by 761
Generation and validation of homozygous fluorescent knock-in cells using CRISPR-Cas9 genome editing
Koch, B., Nijmeijer, B., Kueblbeck, M., Cai, Y., Walther, N., & Ellenberg, J. (2018) · Nature Protocols · doi:10.1038/nprot.2018.042 · Cited by 134
Flagged first, then by citations
Research works printed but not linked: 88
- Sarris, M. & Sixt, M. Science direct navigating in tissue mazes: chemoattractant interpretation in complex environments. Curr. Opin. Cell Biol. 36, 93–102 (2015). · DOI
- Stoitzner, P., Stössel, H., Romani, N. & Pfaller, K. A close-up view of migrating langerhans cells in the skin. J. Investig. Dermatol. 118, 117–125 (2002). · DOI
- Weigelin, B., Bakker, G.-J. & Friedl, P. Intravital third harmonic generation microscopy of collective melanoma cell invasion: principles of interface guidance and microvesicle dynamics. Intravital 1, 32–43 (2012). · DOI
- Diz-Muñoz, A. et al. Steering cell migration by alternating blebs and actin-rich protrusions. BMC Biol. 1–13 https://doi.org/10.1186/s12915-016-0294-x (2016). · DOI
- Fritz-Laylin, L. K. et al. Actin-based protrusions of migrating neutrophils are intrinsically lamellar and facilitate direction changes. Elife 6, 437 (2017).
- Leithner, A. et al. Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nat. Cell Biol. 18, 1253–1259 (2016). · DOI · Paper page
- Baptista, D., Teixeira, L., van Blitterswijk, C., Giselbrecht, S. & Truckenmüller, R. Overlooked? Underestimated? Effects of substrate curvature on cell behavior. Trends Biotechnol. 1–17 https://doi.org/10.1016/j.tibtech.2019.01.006 (2019). · DOI
- Kessels, M. M. & Qualmann, B. Interplay between membrane curvature and the actin cytoskeleton. Curr. Opin. Cell Biol. 68, 10–19 (2021). · DOI
- Carman, P. J. & Dominguez, R. BAR domain proteins-a linkage between cellular membranes, signaling pathways, and the actin cytoskeleton. Biophys. Rev. 10, 1587–1604 (2018). · DOI
- McMahon, H. T. & Gallop, J. L. Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438, 590–596 (2005). · DOI
- Simunovic, M., Voth, G. A., Callan-Jones, A. & Bassereau, P. When physics takes over: BAR proteins and membrane curvature. Trends Cell Biol. 25, 780–792 (2015). · DOI
- de Kreuk, B.-J. & Hordijk, P. L. Control of Rho GTPase function by BAR-domains. Small GTPases 3, 45–52 (2014). · DOI
- Galic, M. et al. External push and internal pull forces recruit curvature-sensing N-BAR domain proteins to the plasma membrane. Nat. Cell Biol. 14, 874–881 (2012). · DOI
- Zhao, W. et al. Nanoscale manipulation of membrane curvature for probing endocytosis in live cells. 1–9 https://doi.org/10.1038/nnano.2017.98 (2017). · DOI
- Lou, H.-Y. et al. Membrane curvature underlies actin reorganization in response to nanoscale surface topography. Proc. Natl Acad. Sci. USA 116, 23143–23151 (2019). · DOI
- Hoogendijk, A. J. et al. Dynamic transcriptome-proteome correlation networks reveal human myeloid differentiation and neutrophil-specific programming. Cell Rep. 29, 2505–2519.e4 (2019). · DOI
- Bhaskara, R. M. et al. Curvature induction and membrane remodeling by FAM134B reticulon homology domain assist selective ER-phagy. Nat. Commun. 1–13 https://doi.org/10.1038/s41467-019-10345-3 (2019). · DOI
- Jensen, L. E. et al. Membrane curvature sensing and stabilization by the autophagic LC3 lipidation machinery. Sci. Adv. 8, eadd1436 (2022). · DOI
- Mahmood, M. I., Noguchi, H. & Okazaki, K.-I. Curvature induction and sensing of the F-BAR protein Pacsin1 on lipid membranes via molecular dynamics simulations. Sci. Rep. 9, 14557–11 (2019). · DOI
- Bigay, J. & Antonny, B. Curvature, lipid packing, and electrostatics of membrane organelles: defining cellular territories in determining specificity. Dev. Cell 23, 886–895 (2012). · DOI
- Mattila, P. K. et al. Missing-in-metastasis and IRSp53 deform PI(4,5)P 2-rich membranes by an inverse BAR domain–like mechanism. J. Cell Biol. 176, 953–964 (2007). · DOI
- Begemann, I. et al. Mechanochemical self-organization determines search pattern in migratory cells. Nat. Phys. 1–13 https://doi.org/10.1038/s41567-019-0505-9 (2020). · DOI
- Pipathsouk, A. et al. The WAVE complex associates with sites of saddle membrane curvature. J. Cell Biol. 220, e202003086 (2021). · DOI
- Weiner, O. D., Marganski, W. A., Wu, L. F., Altschuler, S. J. & Kirschner, M. W. An actin-based wave generator organizes cell motility. PLoS Biol. 5, e221 (2007). · DOI
- Graziano, B. R. et al. A module for Rac temporal signal integration revealed with optogenetics. J. Cell Biol. 216, 2515–2531 (2017). · DOI
- Lacayo, C. I. et al. Emergence of large-scale cell morphology and movement from local actin filament growth dynamics. PLoS Biol. 5, e233 (2007). · DOI
- Berg, S. et al. ilastik: interactive machine learning for (bio)image analysis. Nat. Methods 16, 1226–1232 (2019). · DOI
- Gauthier, N. C., Fardin, M. A., Roca-Cusachs, P. & Sheetz, M. P. Temporary increase in plasma membrane tension coordinates the activation of exocytosis and contraction during cell spreading. Proc. Natl Acad. Sci. USA 108, 14467–14472 (2011). · DOI
- Houk, A. R. et al. Membrane tension maintains cell polarity by confining signals to the leading edge during neutrophil migration. Cell 148, 175–188 (2012). · DOI
- Rocca, D. L., Martin, S., Jenkins, E. L. & Hanley, J. G. Inhibition of Arp2/3-mediated actin polymerization by PICK1 regulates neuronal morphology and AMPA receptor endocytosis. Nat. Cell Biol. 10, 259–271 (2008). · DOI
- Cao, H. et al. FCHSD1 and FCHSD2 are expressed in hair cell stereocilia and cuticular plate and regulate actin polymerization in vitro. PLoS ONE 8, e56516–11 (2013). · DOI
- Kostan, J. et al. Direct interaction of actin filaments with F-BAR protein pacsin2. EMBO Rep. 15, 1154–1162 (2014). · DOI
- Dräger, N. M. et al. Bin1 directly remodels actin dynamics through its BARdomain. EMBO Rep. 18, 2051–2066 (2017). · DOI · Paper page
- Chen, P.-W. et al. The BAR domain of the Arf GTPase-activating protein ASAP1 directly binds actin filaments. J. Biol. Chem. 295, 11303–11315 (2020). · DOI
- Graziano, B. R. et al. Cell confinement reveals a branched-actin independent circuit for neutrophil polarity. PLoS Biol. 17, e3000457–34 (2019). · DOI
- Akin, O. & Mullins, R. D. Capping protein increases the rate of actin-based motility by promoting filament nucleation by the Arp2/3 complex. Cell 133, 841–851 (2008). · DOI
- Cooper, J. A. & Sept, D. New insights into mechanism and regulation of actin capping protein. Int. Rev. Cell Mol. Biol. 267, 183–206 (2008). · DOI
- Edwards, M. et al. Capping protein regulators fine-tune actin assembly dynamics. 1–13 https://doi.org/10.1038/nrm3869 (2014). · DOI
- Funk, J. et al. A barbed end interference mechanism reveals how capping protein promotes nucleation in branched actin networks. Nat. Commun. 1–17 https://doi.org/10.1038/s41467-021-25682-5 (2021). · DOI
- Rao, Y. et al. Molecular basis for SH3 domain regulation of F-BAR-mediated membrane deformation. Proc. Natl Acad. Sci. USA 107, 8213–8218 (2010). · DOI · Paper page
- Kast, D. J. et al. Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and downstream effectors. 1–11 https://doi.org/10.1038/nsmb.2781 (2014). · DOI
- Stanishneva-Konovalova, T. B. et al. Coordinated autoinhibition of F-BAR domain membrane binding and WASp activation by Nervous Wreck. Proc. Natl Acad. Sci. USA 113, E5552–E5561 (2016). · DOI
- Inagaki, N. & Katsuno, H. Actin waves: origin of cell polarization and migration? Trends Cell Biol. 27, 515–526 (2017). · DOI
- Diz-Muñoz, A. et al. Membrane tension acts through PLD2 and mTORC2 to limit actin network assembly during neutrophil migration. PLoS Biol. 14, e1002474–30 (2016). · DOI · Paper page
- Graziano, B. R. et al. Cell confinement reveals a branched-actin independent circuit for neutrophil polarity. PLoS Biol. 17, e3000457 (2019). · DOI
- Renkawitz, J. et al. Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature 568, 546–550 (2019). · DOI
- Yamada, K. M. & Sixt, M. Mechanisms of 3D cell migration. Nat. Rev. Mol. Cell Biol. 1–15 https://doi.org/10.1038/s41580-019-0172-9 (2019). · DOI
- Roycroft, A. & Mayor, R. Molecular basis of contact inhibition of locomotion. Cell. Mol. Life Sci. 73, 1119–1130 (2015). · DOI
- Stramer, B. & Mayor, R. Mechanisms and in vivo functions of contact inhibition of locomotion. Nat. Rev. Mol. Cell Biol. 18, 43–55 (2016). · DOI
- Driscoll, M. K. et al. Cell shape dynamics: from waves to migration. PLoS Comput. Biol. 8, e1002392 (2012). · DOI
- Stankevicins, L. et al. Deterministic actin waves as generators of cell polarization cues. Proc. Natl Acad. Sci. USA 117, 826–835 (2020). · DOI
- Coutinho-Budd, J., Ghukasyan, V., Zylka, M. J. & Polleux, F. The F-BAR domains from srGAP1, srGAP2 and srGAP3 regulate membrane deformation differently. J. Cell Sci. 125, 3390–3401 (2012).
- Guerrier, S. et al. The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis. Cell 138, 990–1004 (2009). · DOI
- Fritz, R. D. et al. SrGAP2-dependent integration of membrane geometry and slit-robo-repulsive cues regulates fibroblast contact inhibition of locomotion. Dev. Cell 35, 78–92 (2015). · DOI
- Ren, C. et al. Leukocyte cytoskeleton polarization is initiated by plasma membrane curvature from cell attachment. Dev. Cell 49, 206–219.e7 (2019). · DOI
- Simunovic, M., Srivastava, A. & Voth, G. A. Linear aggregation of proteins on the membrane as a prelude to membrane remodeling. Proc. Natl Acad. Sci. USA 110, 20396–20401 (2013). · DOI
- Simunovic, M., Šarić, A., Henderson, J. M., Lee, K. Y. C. & Voth, G. A. Long-Range Organization of Membrane-Curving Proteins. ACS Cent. Sci. 3, 1246–1253 (2017). · DOI
- Jarin, Z. et al. Unusual organization of I-BAR proteins on tubular and vesicular membranes. Biophys. J. 117, 553–562 (2019). · DOI
- Nepal, B., Sepehri, A. & Lazaridis, T. Mechanism of negative membrane curvature generation by I-BAR domains. Structure 29, 1440–1452.e4 (2021). · DOI
- Shalem, O. et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343, 84–87 (2014). · DOI · Paper page
- Sanjana, N. E., Shalem, O. & Zhang, F. Improved vectors and genome-wide libraries for CRISPR screening. Nat. Meth. 1–2 https://doi.org/10.1038/nmeth.3047 (2014). · DOI · Paper page
- Axelrod, D. Evanescent excitation and emission in fluorescence microscopy. Biophys. J. 104, 1401–1409 (2013). · DOI
- Anantharam, A., Onoa, B., Edwards, R. H., Holz, R. W. & Axelrod, D. Localized topological changes of the plasma membrane upon exocytosis visualized by polarized TIRFM. J. Cell Biol. 188, 415–428 (2010). · DOI
- Oreopoulos, J., Epand, R. F., Epand, R. M. & Yip, C. M. Peptide-induced domain formation in supported lipid bilayers: direct evidence by combined atomic force and polarized total internal reflection fluorescence microscopy. Biophys. J. 98, 815–823 (2010). · DOI
- Oreopoulos, J. & Yip, C. M. Combined scanning probe and total internal reflection fluorescence microscopy. Methods 46, 2–10 (2008). · DOI
- Sund, S. E., Swanson, J. A. & Axelrod, D. Cell membrane orientation visualized by polarized total internal reflection fluorescence. Biophys. J. 77, 2266–2283 (1999). · DOI
- Axelrod, D. Chapter 7: Total internal reflection fluorescence microscopy. Methods Cell Biol. 89, 169–221 (2008). · DOI
- Meijering, E. et al. Design and validation of a tool for neurite tracing and analysis in fluorescence microscopy images. Cytom. A 58, 167–176 (2004). · DOI
- Renkawitz, J., Reversat, A., Leithner, A., Merrin, J. & Sixt, M. Micro-engineered ‘pillar forests’ to study cell migration in complex but controlled 3D environments. Methods Cell Biol. 147, 79–91 (2018). · DOI
- Kopf, A. et al. Microtubules control cellular shape and coherence in amoeboid migrating cells. J. Cell Biol. 219, 193–24 (2020). · DOI · Paper page
- Sens, P. & Plastino, J. Membrane tension and cytoskeleton organization in cell motility. J. Phys. Condens. Matter 27, 273103 (2015). · DOI
- Hochmuth, F. M., Shao, J. Y., Dai, J. & Sheetz, M. P. Deformation and flow of membrane into tethers extracted from neuronal growth cones. Biophys. J. 70, 358–369 (1996). · DOI
- Franken, H. et al. Thermal proteome profiling for unbiased identification of direct and indirect drug targets using multiplexed quantitative mass spectrometry. Nat. Publ. Group 10, 1567–1593 (2015).
- Perez-Riverol, Y. et al. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucl. Acids Res. 50, D543–D552 (2022). · DOI · Paper page
- Abraham, M. J. et al. GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1-2, 19–25 (2015). · DOI · Paper page
- Marrink, S. J., Risselada, H. J., Yefimov, S., Tieleman, D. P. & de Vries, A. H. The MARTINI force field: coarse grained model for biomolecular simulations. J. Phys. Chem. B 111, 7812–7824 (2007). · DOI
- Monticelli, L. et al. The MARTINI coarse-grained force field: extension to proteins. J. Chem. Theory Comput. 4, 819–834 (2008). · DOI
- Benayad, Z., Bülow, von, S., Stelzl, L. S. & Hummer, G. Simulation of FUS protein condensates with an adapted coarse-grained model. J. Chem. Theory Comput. 17, 525–537 (2021). · DOI
- Periole, X., Cavalli, M., Marrink, S.-J. & Ceruso, M. A. Combining an elastic network with a coarse-grained molecular force field: structure, dynamics, and intermolecular recognition. J. Chem. Theory Comput. 5, 2531–2543 (2009). · DOI
- Wassenaar, T. A., Ingólfsson, H. I., Böckmann, R. A., Tieleman, D. P. & Marrink, S. J. Computational lipidomics with insane: a versatile tool for generating custom membranes for molecular simulations. J. Chem. Theory Comput. 11, 2144–2155 (2015). · DOI · Paper page
- Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., DiNola, A. & Haak, J. R. Molecular dynamics with coupling to an external bath. J. Chem. Phys. 81, 3684 (1998). · DOI
- Bussi, G., Donadio, D. & Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys. 126, 014101 (2007). · DOI
- de Jong, D. H., Baoukina, S., Ingólfsson, H. I. & Marrink, S. J. Martini straight: Boosting performance using a shorter cutoff and GPUs. Comput. Phys. Commun. 199, 1–7 (2016). · DOI
- Parrinello, M. & Rahman, A. Polymorphic transitions in single crystals: a new molecular dynamics method. J. Appl. Phys. 52, 7182 (1998). · DOI
- Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph 14, 33–8–27–8 (1996). · DOI · Paper page
- Gowers, R. et al. in Proceedings of the 15th Python in Science Conference (https://conference.scipy.org/proceedings/scipy2016/oliver_beckstein.html), pp. 98–105 (2016). · DOI
- Michaud-Agrawal, N., Denning, E. J., Woolf, T. B. & Beckstein, O. MDAnalysis: a toolkit for the analysis of molecular dynamics simulations. J. Comput. Chem. 32, 2319–2327 (2011). · DOI
- Titze, B., Genoud, C. & Friedrich, R. W. SBEMimage: versatile acquisition control software for serial block-face electron microscopy. Front. Neural Circuits 12, 54 (2018). · DOI
Metadata
- Authors
- Sitarska, E., Almeida, S. D., Beckwith, M. S., Stopp, J., Czuchnowski, J., Siggel, M., Roessner, R., Tschanz, A., Ejsing, C., Schwab, Y., Kosinski, J., Sixt, M., Kreshuk, A., Erzberger, A., & Diz-Muñoz, A.
- Affiliations
- Heidelberg University (DE)
- European Molecular Biology Laboratory (DE)
- Institute of Science and Technology Austria (AT)
- University of Southern Denmark (DK)
- Corresponding author
- Diz-Muñoz, Alba
- ORCID
- Venue
- Nature Communications
- Published
- 2023-09-13
- Volume
- 14
- Issue
- 1
- Pages
- 5644-5644
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10499897
- OpenAlex
- W3149773180
- Cited by
- 34
- References
- 4
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 6 · 2023: 2
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Desy Publications Database (Deutsches Elektronen-Synchrotron DESY) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron)
- Funders
- European Molecular Biology Laboratory
- Joachim Herz Stiftung
- the BEST program funding by FCT
- the EMBL Interdisciplinary Postdocs (EIPOD) programme under Marie Sklodowska-Curie COFUND actions MSCA-COFUND-FP
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- cell migration, curvature sensing, BAR domain proteins, actin polymerization, cell polarity, cell shape
- MeSH terms
- Actins, Adaptation, Psychological, Biophysics, Cell Membrane, Cell Movement
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