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Mechanically induced topological transition of spectrin regulates its distribution in the mammalian cell cortex

Andrea Ghisleni, Mayte Bonilla-Quintana, Michele Crestani, Zeno Lavagnino, Camilla Galli, Padmini Rangamani () and Nils C. Gauthier ()
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Andrea Ghisleni: The AIRC Institute of Molecular Oncology
Mayte Bonilla-Quintana: University of California San Diego
Michele Crestani: The AIRC Institute of Molecular Oncology
Zeno Lavagnino: The AIRC Institute of Molecular Oncology
Camilla Galli: The AIRC Institute of Molecular Oncology
Padmini Rangamani: University of California San Diego
Nils C. Gauthier: The AIRC Institute of Molecular Oncology

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract The cell cortex is a dynamic assembly formed by the plasma membrane and underlying cytoskeleton. As the main determinant of cell shape, the cortex ensures its integrity during passive and active deformations by adapting cytoskeleton topologies through yet poorly understood mechanisms. The spectrin meshwork ensures such adaptation in erythrocytes and neurons by adopting different organizations. Erythrocytes rely on triangular-like lattices of spectrin tetramers, whereas in neurons they are organized in parallel, periodic arrays. Since spectrin is ubiquitously expressed, we exploited Expansion Microscopy to discover that, in fibroblasts, distinct meshwork densities co-exist. Through biophysical measurements and computational modeling, we show that the non-polarized spectrin meshwork, with the intervention of actomyosin, can dynamically transition into polarized clusters fenced by actin stress fibers that resemble periodic arrays as found in neurons. Clusters experience lower mechanical stress and turnover, despite displaying an extension close to the tetramer contour length. Our study sheds light on the adaptive properties of spectrin, which participates in the protection of the cell cortex by varying its densities in response to key mechanical features.

Date: 2024
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DOI: 10.1038/s41467-024-49906-6

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