Internal Medicine, Gastroenterology and Hepatology, Fondazione Policlinico Universitario, Agostino Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy.
J Microsc. 2020 Dec;280(3):287-296. doi: 10.1111/jmi.12958. Epub 2020 Sep 17.
In physiological conditions, red blood cells (RBCs) are capable of dramatic deformations when passing through the microvasculature. This extreme deformability is closely related to the RBC biconcave shape, to the fluidic nature of the haemoglobin and the cell membrane structure, primarily consisting of a phospholipid bilayer with an underlying two-dimensional spectrin network. In many pathological and inflammatory conditions, the shape and the extreme deformability of erythrocytes appear to be significantly altered. These findings have stimulated intense research towards the search and validation of novel erythrocyte-based mechanical biomarkers, useful for disease diagnosis and therapy monitoring. In this study, we investigated with Atomic Force Microscopy (AFM) the mechanical properties of erythrocytes obtained from a 68 years old cirrhotic man diagnosed with spur cell anaemia and cold agglutinated disease, before and after liver transplantation. Mechanical changes are compared with ultrastructural alterations as studied by scanning electron microscopy and discussed according to confocal fluorescence microscopy results, showing possible alterations induced by the cirrhotic environment at the level of the RBCs cytoskeletal organisation and lipidic composition. Taken together, the results here presented show that liver transplantation not only contributes to restoring the proper RBC morphology, but it also induces recovery of the physiological viscous behaviour of cells, further stressing the relevance of viscous and dissipative forces in determining the RBC biomechanical response.
在生理条件下,红细胞(RBC)在通过微血管时能够发生剧烈的变形。这种极端的变形能力与 RBC 的双凹形形状、血红蛋白的流态性质以及细胞膜结构密切相关,细胞膜结构主要由一个磷脂双层和一个底层二维血影蛋白网络组成。在许多病理和炎症条件下,红细胞的形状和极端变形能力似乎发生了显著改变。这些发现激发了对新型基于红细胞的机械生物标志物的研究和验证,这些标志物可用于疾病诊断和治疗监测。在这项研究中,我们使用原子力显微镜(AFM)研究了一名 68 岁肝硬化男性的红细胞的机械性能,该男性被诊断患有棘状细胞贫血和冷凝集病,在肝移植前后进行了研究。我们将机械变化与扫描电子显微镜研究的超微结构改变进行了比较,并根据共聚焦荧光显微镜结果进行了讨论,结果显示可能是由 RBC 细胞骨架组织和脂质组成的肝硬化环境引起的改变。总之,本文的结果表明,肝移植不仅有助于恢复 RBC 的正常形态,而且还诱导细胞恢复生理粘性行为,进一步强调粘性和耗散力在确定 RBC 生物力学响应中的重要性。