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肝细胞粘弹性特性的多深度定量分析:纳米压痕与有限元建模技术的融合

Multidepth quantitative analysis of liver cell viscoelastic properties: Fusion of nanoindentation and finite element modeling techniques.

作者信息

Zeng Yi, Liu Xianping, Wang Zuobin, Gao Wei, Zhang Shengli, Wang Ying, Liu Yunqing, Yu Haiyue

机构信息

International Research Centre for Nano Handling and Manufacturing of China, Changchun University of Science and Technology, Changchun, China.

Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun, China.

出版信息

Microsc Res Tech. 2025 Jan;88(1):202-212. doi: 10.1002/jemt.24697. Epub 2024 Sep 10.

Abstract

Liver cells are the basic functional unit of the liver. However, repeated or sustained injury leads to structural disorders of liver lobules, proliferation of fibrous tissue and changes in structure, thus increasing scar tissue. Cellular fibrosis affects tissue stiffness, shear force, and other cellular mechanical forces. Mechanical force characteristics can serve as important indicators of cell damage and cirrhosis. Atomic force microscopy (AFM) has been widely used to study cell surface mechanics. However, characterization of the deep mechanical properties inside liver cells remains an underdeveloped field. In this work, cell nanoindentation was combined with finite element analysis to simulate and analyze the mechanical responses of liver cells at different depths in vitro and their internal responses and stress diffusion distributions after being subjected to normal stress. The sensitivities of the visco-hyperelastic parameters of the finite element model to the effects of the peak force and equilibrium force were compared. The force curves of alcohol-damaged liver cells at different depths were measured and compared with those of undamaged liver cells. The inverse analysis method was used to simulate the finite element model in vitro. Changes in the parameters of the cell model after injury were explored and analyzed, and their potential for characterizing hepatocellular injury and related treatments was evaluated. RESEARCH HIGHLIGHTS: This study aims to establish an in vitro hyperelastic model of liver cells and analyze the mechanical changes of cells in vitro. An analysis method combining finite element analysis model and nanoindentation was used to obtain the key parameters of the model. The multi-depth mechanical differences and internal structural changes of injured liver cells were analyzed.

摘要

肝细胞是肝脏的基本功能单位。然而,反复或持续的损伤会导致肝小叶结构紊乱、纤维组织增生及结构改变,进而增加瘢痕组织。细胞纤维化会影响组织硬度、剪切力及其他细胞机械力。机械力特性可作为细胞损伤和肝硬化的重要指标。原子力显微镜(AFM)已被广泛用于研究细胞表面力学。然而,肝细胞内部深层力学特性的表征仍是一个未充分发展的领域。在这项工作中,将细胞纳米压痕与有限元分析相结合,以模拟和分析体外不同深度肝细胞的力学响应,以及在承受法向应力后它们的内部响应和应力扩散分布。比较了有限元模型的粘弹性超弹性参数对峰值力和平衡力作用的敏感性。测量了不同深度酒精损伤肝细胞的力曲线,并与未损伤肝细胞的力曲线进行比较。采用反分析方法对体外有限元模型进行模拟。探索并分析了损伤后细胞模型参数的变化,并评估了它们在表征肝细胞损伤及相关治疗方面的潜力。研究亮点:本研究旨在建立体外肝细胞超弹性模型并分析体外细胞的力学变化。采用有限元分析模型与纳米压痕相结合的分析方法获取模型的关键参数。分析了损伤肝细胞的多深度力学差异及内部结构变化。

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