Article Dans Une Revue Biophysical Journal Année : 2025

The mechanism of nesprin-2 accumulation at the nucleus front during confined cell migration

Inge Bos
Sirine Amiri
Thierry Dubois
Alain Karma
Vincent Hakim

Résumé

Cell migration through constrictions is essential for many physiological processes. During this confined cell migration the protein nesprin-2, which links the cytoskeletal network to the nucleus, can accumulate at the front of the nucleus. Yet, up to now, the exact mechanism of this accumulation is unknown. Here, we further investigate this accumulation mechanism. We quantify the spatial distribution of nesprin-2, actin and the proteins SUN1 and SUN2, which are inner nuclear membrane proteins that bind to nesprin-2. We observe that SUN2 shows the same frontal accumulation as nesprin-2, but SUN1 does not. Based on the spatial protein distributions and the homology between the actin binding domains of nesprin-2 and the well characterised actin binding protein α-actinin-4, we hypothesise that strengthening of the nesprin-actin bond upon increasing actin pulling force induces frontal nesprin-2 accumulation. This forcestrengthening behaviour is known as catch bond binding. Based on this catch bond hypothesis we develop a simple physical model that qualitatively reproduces the experimentally observed nesprin-2 profiles. We try to further test the catch bond hypothesis by using a specific point mutation to abrogate the catch bond behaviour in mininesprin-2 constructs. These chimeric constructs consist of the N-terminal actin binding domains and the C-terminal SUN binding domain of nesprin-2. The experimentally measured distribution of the mininesprin-2 mutant agrees well with the model prediction on this mutation effect. All in all, our work builds an important foundation to unravel the mechanism of frontal nesprin-2 accumulation during confined cell migration.

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DOI

Cite 10.5281/zenodo.13829265 Jeu de données Bos, I., Amiri, S., Maire, V., Dubois, T., Karma, A., Hakim, V., & Sykes, C. (2025). Dataset for ‘The mechanism of nesprin-2 accumulation at the nucleus front during confined cell migration’ [Data set]. Zenodo. https://doi.org/10.5281/ZENODO.13829265

Dates et versions

hal-05077888 , version 1 (21-05-2025)

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Inge Bos, Sirine Amiri, Virginie Maire, Thierry Dubois, Alain Karma, et al.. The mechanism of nesprin-2 accumulation at the nucleus front during confined cell migration. Biophysical Journal, 2025, 124 (12), pp.2056-2069. ⟨10.1016/j.bpj.2025.05.003⟩. ⟨hal-05077888⟩
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