Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles

Ewa Sitarska, Silvia Dias Almeida, Marianne Sandvold Beckwith, Julian Stopp, Jakub Czuchnowski, Marc Siggel, Rita Roessner, Aline Tschanz, Christer Ejsing, Yannick Schwab, Jan Kosinski, Michael Sixt, Anna Kreshuk, Anna Erzberger and Alba Diz-Muñoz ()
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Ewa Sitarska: European Molecular Biology Laboratory
Silvia Dias Almeida: European Molecular Biology Laboratory
Marianne Sandvold Beckwith: European Molecular Biology Laboratory
Julian Stopp: Institute of Science and Technology Austria
Jakub Czuchnowski: European Molecular Biology Laboratory
Marc Siggel: European Molecular Biology Laboratory
Rita Roessner: European Molecular Biology Laboratory
Aline Tschanz: European Molecular Biology Laboratory
Christer Ejsing: European Molecular Biology Laboratory
Yannick Schwab: European Molecular Biology Laboratory
Jan Kosinski: European Molecular Biology Laboratory
Michael Sixt: Institute of Science and Technology Austria
Anna Kreshuk: European Molecular Biology Laboratory
Anna Erzberger: European Molecular Biology Laboratory
Alba Diz-Muñoz: European Molecular Biology Laboratory

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41173-1

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