Cited by 34Cellular Mechanics and InteractionsCellular transport and secretionLipid Membrane Structure and Behavior

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Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles

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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.

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  1. Sarris, M. & Sixt, M. Science direct navigating in tissue mazes: chemoattractant interpretation in complex environments. Curr. Opin. Cell Biol. 36, 93–102 (2015). · DOI
  2. 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
  3. 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
  4. 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
  5. Fritz-Laylin, L. K. et al. Actin-based protrusions of migrating neutrophils are intrinsically lamellar and facilitate direction changes. Elife 6, 437 (2017).
  6. 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
  7. 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
  8. Kessels, M. M. & Qualmann, B. Interplay between membrane curvature and the actin cytoskeleton. Curr. Opin. Cell Biol. 68, 10–19 (2021). · DOI
  9. 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
  10. McMahon, H. T. & Gallop, J. L. Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438, 590–596 (2005). · DOI
  11. 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
  12. de Kreuk, B.-J. & Hordijk, P. L. Control of Rho GTPase function by BAR-domains. Small GTPases 3, 45–52 (2014). · DOI
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. Jensen, L. E. et al. Membrane curvature sensing and stabilization by the autophagic LC3 lipidation machinery. Sci. Adv. 8, eadd1436 (2022). · DOI
  19. 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
  20. 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
  21. 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
  22. 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
  23. Pipathsouk, A. et al. The WAVE complex associates with sites of saddle membrane curvature. J. Cell Biol. 220, e202003086 (2021). · DOI
  24. 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
  25. Graziano, B. R. et al. A module for Rac temporal signal integration revealed with optogenetics. J. Cell Biol. 216, 2515–2531 (2017). · DOI
  26. 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
  27. Berg, S. et al. ilastik: interactive machine learning for (bio)image analysis. Nat. Methods 16, 1226–1232 (2019). · DOI
  28. 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
  29. 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
  30. 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
  31. 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
  32. Kostan, J. et al. Direct interaction of actin filaments with F-BAR protein pacsin2. EMBO Rep. 15, 1154–1162 (2014). · DOI
  33. Dräger, N. M. et al. Bin1 directly remodels actin dynamics through its BARdomain. EMBO Rep. 18, 2051–2066 (2017). · DOI · Paper page
  34. 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
  35. Graziano, B. R. et al. Cell confinement reveals a branched-actin independent circuit for neutrophil polarity. PLoS Biol. 17, e3000457–34 (2019). · DOI
  36. 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
  37. 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
  38. Edwards, M. et al. Capping protein regulators fine-tune actin assembly dynamics. 1–13 https://doi.org/10.1038/nrm3869 (2014). · DOI
  39. 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
  40. 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
  41. 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
  42. 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
  43. Inagaki, N. & Katsuno, H. Actin waves: origin of cell polarization and migration? Trends Cell Biol. 27, 515–526 (2017). · DOI
  44. 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
  45. Graziano, B. R. et al. Cell confinement reveals a branched-actin independent circuit for neutrophil polarity. PLoS Biol. 17, e3000457 (2019). · DOI
  46. Renkawitz, J. et al. Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature 568, 546–550 (2019). · DOI
  47. 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
  48. Roycroft, A. & Mayor, R. Molecular basis of contact inhibition of locomotion. Cell. Mol. Life Sci. 73, 1119–1130 (2015). · DOI
  49. Stramer, B. & Mayor, R. Mechanisms and in vivo functions of contact inhibition of locomotion. Nat. Rev. Mol. Cell Biol. 18, 43–55 (2016). · DOI
  50. Driscoll, M. K. et al. Cell shape dynamics: from waves to migration. PLoS Comput. Biol. 8, e1002392 (2012). · DOI
  51. Stankevicins, L. et al. Deterministic actin waves as generators of cell polarization cues. Proc. Natl Acad. Sci. USA 117, 826–835 (2020). · DOI
  52. 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).
  53. 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
  54. 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
  55. Ren, C. et al. Leukocyte cytoskeleton polarization is initiated by plasma membrane curvature from cell attachment. Dev. Cell 49, 206–219.e7 (2019). · DOI
  56. 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
  57. 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
  58. Jarin, Z. et al. Unusual organization of I-BAR proteins on tubular and vesicular membranes. Biophys. J. 117, 553–562 (2019). · DOI
  59. Nepal, B., Sepehri, A. & Lazaridis, T. Mechanism of negative membrane curvature generation by I-BAR domains. Structure 29, 1440–1452.e4 (2021). · DOI
  60. Shalem, O. et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343, 84–87 (2014). · DOI · Paper page
  61. 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
  62. Axelrod, D. Evanescent excitation and emission in fluorescence microscopy. Biophys. J. 104, 1401–1409 (2013). · DOI
  63. 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
  64. 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
  65. Oreopoulos, J. & Yip, C. M. Combined scanning probe and total internal reflection fluorescence microscopy. Methods 46, 2–10 (2008). · DOI
  66. 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
  67. Axelrod, D. Chapter 7: Total internal reflection fluorescence microscopy. Methods Cell Biol. 89, 169–221 (2008). · DOI
  68. 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
  69. 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
  70. Kopf, A. et al. Microtubules control cellular shape and coherence in amoeboid migrating cells. J. Cell Biol. 219, 193–24 (2020). · DOI · Paper page
  71. Sens, P. & Plastino, J. Membrane tension and cytoskeleton organization in cell motility. J. Phys. Condens. Matter 27, 273103 (2015). · DOI
  72. 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
  73. 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).
  74. 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
  75. 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
  76. 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
  77. Monticelli, L. et al. The MARTINI coarse-grained force field: extension to proteins. J. Chem. Theory Comput. 4, 819–834 (2008). · DOI
  78. 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
  79. 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
  80. 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
  81. 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
  82. Bussi, G., Donadio, D. & Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys. 126, 014101 (2007). · DOI
  83. 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
  84. Parrinello, M. & Rahman, A. Polymorphic transitions in single crystals: a new molecular dynamics method. J. Appl. Phys. 52, 7182 (1998). · DOI
  85. Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph 14, 33–8–27–8 (1996). · DOI · Paper page
  86. 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
  87. 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
  88. 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
Venue
Nature Communications
Published
2023-09-13
Volume
14
Issue
1
Pages
5644-5644
ISSN
2041-1723 (ISSN-L)
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
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

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