Hoffmann Patrick C, Kim Hyuntae, Obarska-Kosinska Agnieszka, Kreysing Jan Philipp, Andino-Frydman Eli, Cruz-León Sergio, Margiotta Erica, Cernikova Lenka, Kosinski Jan, Turoňová Beata, Hummer Gerhard, Beck Martin
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, 60438 Frankfurt am Main, Germany.
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, 60438 Frankfurt am Main, Germany; IMPRS on Cellular Biophysics, Max-von-Laue-Straße 3, 60438 Frankfurt am Main, Germany.
Mol Cell. 2025 Feb 6;85(3):537-554.e11. doi: 10.1016/j.molcel.2024.11.038. Epub 2024 Dec 26.
Changing environmental conditions necessitate rapid adaptation of cytoplasmic and nuclear volumes. We use the slime mold Dictyostelium discoideum, known for its ability to tolerate extreme changes in osmolarity, to assess which role nuclear pore complexes (NPCs) play in achieving nuclear volume adaptation and relieving mechanical stress. We capitalize on the unique properties of D. discoideum to quantify fluid flow across NPCs. D. discoideum has an elaborate NPC structure in situ. Its dilation state affects NPC permeability for nucleocytosolic flow. Based on mathematical concepts adapted from hydrodynamics, we conceptualize this phenomenon as porous flow across NPCs, which is distinct from canonically characterized modes of nucleocytoplasmic transport because of its dependence on pressure. Viral NPC blockage decreased nucleocytosolic flow. Our results may be relevant for any biological conditions that entail rapid nuclear size adaptation, including metastasizing cancer cells, migrating cells, or differentiating tissues.
不断变化的环境条件要求细胞质和细胞核体积迅速适应。我们利用以能够耐受渗透压的极端变化而闻名的黏菌盘基网柄菌,来评估核孔复合体(NPC)在实现细胞核体积适应和缓解机械应力中所起的作用。我们利用盘基网柄菌的独特特性来量化穿过NPC的流体流动。盘基网柄菌在原位具有精细的NPC结构。其扩张状态影响NPC对核质流动的通透性。基于从流体动力学改编而来的数学概念,我们将这一现象概念化为穿过NPC的多孔流动,由于其对压力的依赖性,这与典型特征的核质运输模式不同。病毒对NPC的阻断减少了核质流动。我们的结果可能与任何需要细胞核大小快速适应的生物学条件相关,包括转移癌细胞、迁移细胞或分化组织。