Paraschiv, Alexandru; Lagny, Thibaut J.; Campos, Christian Vanhille; Coudrier, Evelyne; Bassereau, Patricia; Šarić, AnđelaISTA
The cell membrane is an inhomogeneous system composed of phospholipids, sterols, carbohydrates, and proteins that can be directly attached to underlying cytoskeleton. The protein linkers between the membrane and the cytoskeleton are believed to have a profound effect on the mechanical properties of the cell membrane and its ability to reshape. Here, we investigate the role of membrane-cortex linkers on the extrusion of membrane tubes using computer simulations and experiments. In simulations, we find that the force for tube extrusion has a nonlinear dependence on the density of membrane-cortex attachments: at a range of low and intermediate linker densities, the force is not significantly influenced by the presence of the membrane-cortex attachments and resembles that of the bare membrane. For large concentrations of linkers, however, the force substantially increases compared with the bare membrane. In both cases, the linkers provided membrane tubes with increased stability against coalescence. We then pulled tubes from HEK cells using optical tweezers for varying expression levels of the membrane-cortex attachment protein Ezrin. In line with simulations, we observed that overexpression of Ezrin led to an increased extrusion force, while Ezrin depletion had a negligible effect on the force. Our results shed light on the importance of local protein rearrangements for membrane reshaping at nanoscopic scales.
We thank Ewa Paluch, Alba Diz-Muñoz, Guillaume Salbreux, Guillaume Charras, and Shiladitya Banerjee for helpful discussions. We acknowledge support from the Engineering and Physical Sciences Research Council (A.P. and A.Š.), the UCL Institute for the Physics of Living Systems (A.P., C.V.C., and A.Š.), the Royal Society (C.V.C. and A.Š.), and the European Research Council (Starting grant EP/R011818/1 to A.Š.; E.C. and P.B. are partners of the advanced grant, project 339847) and from Institut Curie (E.C. and P.B.) and Centre National de la Recherche Scientifique (CNRS) (E.C. and P.B.). The P.B. and E.C. groups belong to Labex CelTisPhyBio (ANR-11-LABX0038) and to Paris Sciences et Lettres (ANR-10-IDEX-0001-02). T.L. received a PhD grant from Paris Sciences et Lettres Research University and support from the Institut Curie.
Paraschiv A, Lagny TJ, Campos CV, Coudrier E, Bassereau P, Šarić A. Influence of membrane-cortex linkers on the extrusion of membrane tubes. Biophysical Journal. 2021;120(4):598-606. doi:10.1016/j.bpj.2020.12.028
Paraschiv, A., Lagny, T. J., Campos, C. V., Coudrier, E., Bassereau, P., & Šarić, A. (2021). Influence of membrane-cortex linkers on the extrusion of membrane tubes. Biophysical Journal. Cell Press. https://doi.org/10.1016/j.bpj.2020.12.028
Paraschiv, Alexandru, Thibaut J. Lagny, Christian Vanhille Campos, Evelyne Coudrier, Patricia Bassereau, and Anđela Šarić. “Influence of Membrane-Cortex Linkers on the Extrusion of Membrane Tubes.” Biophysical Journal. Cell Press, 2021. https://doi.org/10.1016/j.bpj.2020.12.028.
A. Paraschiv, T. J. Lagny, C. V. Campos, E. Coudrier, P. Bassereau, and A. Šarić, “Influence of membrane-cortex linkers on the extrusion of membrane tubes,” Biophysical Journal, vol. 120, no. 4. Cell Press, pp. 598–606, 2021.
Paraschiv A, Lagny TJ, Campos CV, Coudrier E, Bassereau P, Šarić A. 2021. Influence of membrane-cortex linkers on the extrusion of membrane tubes. Biophysical Journal. 120(4), 598–606.
Paraschiv, Alexandru, et al. “Influence of Membrane-Cortex Linkers on the Extrusion of Membrane Tubes.” Biophysical Journal, vol. 120, no. 4, Cell Press, 2021, pp. 598–606, doi:10.1016/j.bpj.2020.12.028.