乌普萨拉大学Taija Mäkinen研究组取得一项新突破。他们揭示了细胞形状的动态细胞骨架调节支持淋巴内皮的弹性。相关论文于2025年3月19日发表在《自然》杂志上。

在这里，研究小组确定了由各向同性拉伸诱导的LEC形状的动态细胞骨架调节，这对真皮淋巴毛细血管的完整性和功能至关重要。研究团队发现，橡树叶状的LECs在小叶细胞间界面显示出基于VE-钙粘蛋白的连接结构光谱和独特的细胞骨架组织，微管位于凹区，F-肌动蛋白位于凸叶。毛细血管LEC形状和肌动蛋白的多光谱和纵向活体成像显示，在体内稳态和响应间质液容量增加时，细胞重叠的动态重构。与植物表皮的拼图细胞类似，LEC的形状由Rho GTPase CDC42调控的细胞骨架动力学控制，增强了单层的稳定性。此外，循环各向同性拉伸增加了初级LECs的细胞重叠和结曲率。

他们的研究结果表明，毛细血管LEC形状是由细胞重叠的持续重塑造成的，这些重叠维持了血管的完整性，同时保持了与血管扩张和液体摄取相容的渗透性细胞-细胞接触。该课题组人员提出了一种类似于波纹管的流体推进机制，在这种机制中，流体诱导的LEC重叠的管腔扩张和收缩被基于肌动蛋白的板足样重叠扩展所抵消，以帮助血管收缩。

研究人员表示，淋巴毛细血管不断地吸收间质液，并适应由此产生的血管口径变化。松散连接淋巴内皮细胞（LECs）4的可渗透单层维持机械稳定性的机制尚不清楚。

附：英文原文

Title: Dynamic cytoskeletal regulation of cell shape supports resilience of lymphatic endothelium

Author: Schoofs, Hans, Daubel, Nina, Schnabellehner, Sarah, Grnloh, Max L. B., Palacios Martnez, Sebastin, Halme, Aleksi, Marks, Amanda M., Jeansson, Marie, Barcos, Sara, Brakebusch, Cord, Benedito, Rui, Engelhardt, Britta, Vestweber, Dietmar, Gaengel, Konstantin, Linsenmeier, Fabian, Schrmann, Sebastian, Saharinen, Pipsa, van Buul, Jaap D., Friedrich, Oliver, Smith, Richard S., Majda, Mateusz, Mkinen, Taija

Issue&Volume: 2025-03-19

Abstract: Lymphatic capillaries continuously take up interstitial fluid and adapt to resulting changes in vessel calibre1,2,3. The mechanisms by which the permeable monolayer of loosely connected lymphatic endothelial cells (LECs)4 maintains mechanical stability remain elusive. Here we identify dynamic cytoskeletal regulation of LEC shape, induced by isotropic stretch, as crucial for the integrity and function of dermal lymphatic capillaries. We found that the oak leaf-shaped LECs showed a spectrum of VE-cadherin-based junctional configurations at the lobular intercellular interface and a unique cytoskeletal organization, with microtubules at concave regions and F-actin at convex lobes. Multispectral and longitudinal intravital imaging of capillary LEC shape and actin revealed dynamic remodelling of cellular overlaps in vivo during homeostasis and in response to interstitial fluid volume increase. Akin to puzzle cells of the plant epidermis5,6, LEC shape was controlled by Rho GTPase CDC42-regulated cytoskeletal dynamics, enhancing monolayer stability. Moreover, cyclic isotropic stretch increased cellular overlaps and junction curvature in primary LECs. Our findings indicate that capillary LEC shape results from continuous remodelling of cellular overlaps that maintain vessel integrity while preserving permeable cell–cell contacts compatible with vessel expansion and fluid uptake. We propose a bellows-like fluid propulsion mechanism, in which fluid-induced lumen expansion and shrinkage of LEC overlaps are countered by actin-based lamellipodia-like overlap extension to aid vessel constriction.

DOI: 10.1038/s41586-025-08724-6

Source: https://www.nature.com/articles/s41586-025-08724-6