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Fission of double-membrane tubes under tension
Biophysical Journal ( IF 3.2 ) Pub Date : 2024-10-15 , DOI: 10.1016/j.bpj.2024.10.009 Russell K.W. Spencer, Isaac Santos-Pérez, Anna V. Shnyrova, Marcus Müller
Biophysical Journal ( IF 3.2 ) Pub Date : 2024-10-15 , DOI: 10.1016/j.bpj.2024.10.009 Russell K.W. Spencer, Isaac Santos-Pérez, Anna V. Shnyrova, Marcus Müller
The division of a cellular compartment culminates with the scission of a highly constricted membrane neck. Scission requires lipid rearrangements, topology changes, and transient formation of nonbilayer intermediate structures driven by curvature stress. Often, a side effect of this stress is pore-formation, which may lead to content leakage and thus breaching of the membrane barrier function. In single-membrane systems, leakage is avoided through the formation of a hemifusion (HF) intermediate, whose structure is still a subject of debate. The consequences of curvature stress have not been explored in double-membrane systems, such as the mitochondrion. Here, we combine experimental and theoretical approaches to study neck constriction and scission driven by tension in biomimetic lipid systems, namely single- and double-membrane nanotubes (sNTs and dNTs), respectively. In sNTs, constriction by high tension gives rise to a metastable HF intermediate (seen as stalk or worm-like micelle), whereas poration is universally slower in a simple neck. In dNTs, high membrane tension causes sequential rupture of each membrane. In contrast, low tension leads to the HF of both membranes, which may lead to a leaky fusion pathway, or may progress to further fusion of the two membranes along a number of transformation pathways. These findings provide a new mechanistic basis for fundamental cellular processes.
中文翻译:
双膜管在张力作用下的裂变
细胞隔室的分裂以高度收缩的膜颈的断裂而告终。断裂需要脂质重排、拓扑变化和由曲率应力驱动的非双层中间结构的瞬时形成。通常,这种应力的副作用是孔形成,这可能导致内容物泄漏,从而破坏膜屏障功能。在单膜系统中,通过形成半融合 (HF) 中间体来避免泄漏,其结构仍然是一个争论的话题。曲率应力的后果尚未在双膜系统(例如线粒体)中得到探索。在这里,我们结合了实验和理论方法来研究仿生脂质系统(即单膜和双膜纳米管 (sNTs 和 dNTs))中由张力驱动的颈部收缩和断裂。在 sNT 中,高张力的收缩会产生亚稳态 HF 中间体(被视为茎状或蠕虫状胶束),而在简单的颈部中,孔隙通常较慢。在 dNT 中,高膜张力会导致每个膜连续破裂。相反,低张力导致两个膜的 HF,这可能导致渗漏的融合途径,或者可能沿着许多转化途径发展为两个膜的进一步融合。这些发现为基本细胞过程提供了新的机制基础。
更新日期:2024-10-15
中文翻译:
双膜管在张力作用下的裂变
细胞隔室的分裂以高度收缩的膜颈的断裂而告终。断裂需要脂质重排、拓扑变化和由曲率应力驱动的非双层中间结构的瞬时形成。通常,这种应力的副作用是孔形成,这可能导致内容物泄漏,从而破坏膜屏障功能。在单膜系统中,通过形成半融合 (HF) 中间体来避免泄漏,其结构仍然是一个争论的话题。曲率应力的后果尚未在双膜系统(例如线粒体)中得到探索。在这里,我们结合了实验和理论方法来研究仿生脂质系统(即单膜和双膜纳米管 (sNTs 和 dNTs))中由张力驱动的颈部收缩和断裂。在 sNT 中,高张力的收缩会产生亚稳态 HF 中间体(被视为茎状或蠕虫状胶束),而在简单的颈部中,孔隙通常较慢。在 dNT 中,高膜张力会导致每个膜连续破裂。相反,低张力导致两个膜的 HF,这可能导致渗漏的融合途径,或者可能沿着许多转化途径发展为两个膜的进一步融合。这些发现为基本细胞过程提供了新的机制基础。