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.
We thank Jan Ellenberg, Leanne Strauss, Anusha Gopalan, and Jia Hui Li for critical feedback on the manuscript and the Life Science Editors for editing assistance. The plasmid with hSnx33 was a kind gift from Duanqing Pei. Cell line with GFP-tagged IRSp53 was a kind gift from Orion Weiner. We thank Brian Graziano for providing protocols, reagents, and key advice to generate CRISPR knockout HL-60 cells. We thank the EMBL flow cytometry core facility, the EMBL advanced light microscopy facility, the EMBL proteomics facility, and the EMBL genomics core facility for support and advice. We thank Anusha Gopalan and Martin Bergert for their support during mechanical measurements by AFM. We thank Estela Sosa Osorio for technical assistance for the co-immunoprecipitation. We thank the EMBL genome biology computational support (and specially Charles Girardot and Jelle Scholtalbers) for critical assistance during RNAseq analysis. We thank Hans Kristian Hannibal‐Bach for his technical assistance during the lipidomic analysis of plasma membrane isolates. We thank Steffen Burgold for their support with LLS7 microscope in the ZEISS Microscopy Customer Center Europe. We acknowledge the financial support of the European Molecular Biology Laboratory (EMBL) to A.D.-M., Y.S., A.K., and A.E., the EMBL Interdisciplinary Postdocs (EIPOD) program under Marie Sklodowska-Curie COFUND actions MSCA-COFUND-FP to M.S.B. and M. S. (grant agreement number: 847543), the BEST program funding by FCT (SFRH/BEST/150300/2019) to S.D.A. and the Joachim Herz Stiftung Add-on Fellowship for Interdisciplinary Science to E.S. Open Access funding enabled and organized by Projekt DEAL.
Sitarska E, Almeida SD, Beckwith MS, et al. Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles. Nature Communications. 2023;14. doi:10.1038/s41467-023-41173-1
Sitarska, E., Almeida, S. D., Beckwith, M. S., Stopp, J. A., Czuchnowski, J., Siggel, M., … Diz-Muñoz, A. (2023). Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-023-41173-1
Sitarska, Ewa, Silvia Dias Almeida, Marianne Sandvold Beckwith, Julian A Stopp, Jakub Czuchnowski, Marc Siggel, Rita Roessner, et al. “Sensing Their Plasma Membrane Curvature Allows Migrating Cells to Circumvent Obstacles.” Nature Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-41173-1.
E. Sitarska et al., “Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles,” Nature Communications, vol. 14. Springer Nature, 2023.
Sitarska E, Almeida SD, Beckwith MS, Stopp JA, Czuchnowski J, Siggel M, Roessner R, Tschanz A, Ejsing C, Schwab Y, Kosinski J, Sixt MK, Kreshuk A, Erzberger A, Diz-Muñoz A. 2023. Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles. Nature Communications. 14, 5644.
Sitarska, Ewa, et al. “Sensing Their Plasma Membrane Curvature Allows Migrating Cells to Circumvent Obstacles.” Nature Communications, vol. 14, 5644, Springer Nature, 2023, doi:10.1038/s41467-023-41173-1.
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