Zapotoczny Bartlomiej, Braet Filip, Wisse Eddie, Lekka Malgorzata, Szymonski Marek
Institute of Nuclear Physics, Polish Academy of Sciences, 31-342, Krakow, Poland.
Faculty of Medicine and Health, School of Medical Sciences (Discipline of Anatomy and Histology), The University of Sydney, Sydney, NSW, 2006, Australia.
Biophys Rev. 2020 Jun;12(3):625-636. doi: 10.1007/s12551-020-00699-0. Epub 2020 May 18.
The structural-functional hallmark of the liver sinusoidal endothelium is the presence of fenestrae grouped in sieve plates. Fenestrae are open membrane bound pores supported by a (sub)membranous cytoskeletal lattice. Changes in number and diameter of fenestrae alter bidirectional transport between the sinusoidal blood and the hepatocytes. Their physiological relevance has been shown in different liver disease models. Although the structural organization of fenestrae has been well documented using different electron microscopy approaches, the dynamic nature of those pores remained an enigma until the recent developments in the research field of four dimensional (4-D) AFM. In this contribution we highlight how AFM as a biophysical nanocharacterization tool enhanced our understanding in the dynamic behaviour of liver sinusoidal endothelial fenestrae. Different AFM probing approaches, including spectroscopy, enabled mapping of topography and nanomechanical properties at unprecedented resolution under live cell imaging conditions. This dynamic biophysical characterization approach provided us with novel information on the 'short' life-span, formation, disappearance and closure of hepatic fenestrae. These observations are briefly reviewed against the existing literature.
肝窦内皮细胞的结构-功能特征是存在聚集在筛板中的窗孔。窗孔是由（亚）膜性细胞骨架晶格支撑的开放的膜结合孔。窗孔数量和直径的变化会改变窦状隙血液与肝细胞之间的双向运输。它们的生理相关性已在不同的肝病模型中得到证实。尽管使用不同的电子显微镜方法对窗孔的结构组织已有充分记录，但直到四维（4-D）原子力显微镜研究领域的最新进展，这些孔的动态性质仍然是个谜。在本论文中，我们强调了原子力显微镜作为一种生物物理纳米表征工具如何增强了我们对肝窦内皮窗孔动态行为的理解。不同的原子力显微镜探测方法，包括光谱学，能够在活细胞成像条件下以前所未有的分辨率绘制形貌和纳米力学特性图。这种动态生物物理表征方法为我们提供了有关肝窗孔“短暂”寿命、形成、消失和闭合的新信息。对照现有文献对这些观察结果进行了简要综述。
