澳大利亚昆士兰大学Samantha J. Stehbens等研究人员合作发现，压缩依赖性微管强化使细胞能够在受限环境中导航。相关论文于2024年8月19日在线发表在《自然—细胞生物学》杂志上。

研究人员展示了压缩会触发细胞核后方特定微管结构的强化，这一过程通过机械响应性招募细胞质连接蛋白相关蛋白来动态增强和修复微管结构。这些强化的微管形成了机械稳态装置：一种自适应反馈机制，使细胞既能抵抗压缩力，又能时空组织收缩信号通路。

微管机械稳态装置有助于细胞核的定位，并协调力的产生，使细胞能够通过狭窄的空间。机械稳态装置的破坏会导致皮质收缩力失衡，迁移停止，最终导致细胞破裂。该研究揭示了微管作为细胞传感器的作用，它们能够检测和响应压缩力，从而促进运动并确保在机械要求苛刻的环境中生存。

据介绍，细胞在通过复杂的三维环境中迁移时，会面临巨大的物理挑战，包括拉伸应力和压缩力。为了移动，细胞需要抵抗这些力，同时还要将大的细胞核挤压通过狭窄的空间。这需要高度协调的皮质收缩力。微管不仅能够抵抗压缩力，还能隔离关键的肌动蛋白-肌球蛋白调节因子，以确保适当的收缩力激活。然而，在三维环境中，这两种作用如何整合以实现核迁移在很大程度上仍不清楚。

附：英文原文

Title: Compression-dependent microtubule reinforcement enables cells to navigate confined environments

Author: Ju, Robert J., Falconer, Alistair D., Schmidt, Christanny J., Enriquez Martinez, Marco A., Dean, Kevin M., Fiolka, Reto P., Sester, David P., Nobis, Max, Timpson, Paul, Lomakin, Alexis J., Danuser, Gaudenz, White, Melanie D., Haass, Nikolas K., Oelz, Dietmar B., Stehbens, Samantha J.

Issue&Volume: 2024-08-19

Abstract: Cells migrating through complex three-dimensional environments experience considerable physical challenges, including tensile stress and compression. To move, cells need to resist these forces while also squeezing the large nucleus through confined spaces. This requires highly coordinated cortical contractility. Microtubules can both resist compressive forces and sequester key actomyosin regulators to ensure appropriate activation of contractile forces. Yet, how these two roles are integrated to achieve nuclear transmigration in three dimensions is largely unknown. Here, we demonstrate that compression triggers reinforcement of a dedicated microtubule structure at the rear of the nucleus by the mechanoresponsive recruitment of cytoplasmic linker-associated proteins, which dynamically strengthens and repairs the lattice. These reinforced microtubules form the mechanostat: an adaptive feedback mechanism that allows the cell to both withstand compressive force and spatiotemporally organize contractility signalling pathways. The microtubule mechanostat facilitates nuclear positioning and coordinates force production to enable the cell to pass through constrictions. Disruption of the mechanostat imbalances cortical contractility, stalling migration and ultimately resulting in catastrophic cell rupture. Our findings reveal a role for microtubules as cellular sensors that detect and respond to compressive forces, enabling movement and ensuring survival in mechanically demanding environments.

DOI: 10.1038/s41556-024-01476-x

Source: https://www.nature.com/articles/s41556-024-01476-x