原子力显微镜(AFM)在致心律失常性心肌病中的应用。

Atomic Force Microscopy (AFM) Applications in Arrhythmogenic Cardiomyopathy.

机构信息

CU-Cardiovascular Institute, University of Colorado Anschutz Medical Campus, 12700 East 19th Ave., Aurora, CO 80045, USA.

Department of Bioengineering, University of Colorado Anschutz Medical Campus, 12700 East 19th Ave., Aurora, CO 80045, USA.

出版信息

Int J Mol Sci. 2022 Mar 28;23(7):3700. doi: 10.3390/ijms23073700.

Abstract

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by progressive replacement of cardiomyocytes by fibrofatty tissue, ventricular dilatation, cardiac dysfunction, arrhythmias, and sudden cardiac death. Interest in molecular biomechanics for these disorders is constantly growing. Atomic force microscopy (AFM) is a well-established technic to study the mechanobiology of biological samples under physiological and pathological conditions at the cellular scale. However, a review which described all the different data that can be obtained using the AFM (cell elasticity, adhesion behavior, viscoelasticity, beating force, and frequency) is still missing. In this review, we will discuss several techniques that highlight the potential of AFM to be used as a tool for assessing the biomechanics involved in ACM. Indeed, analysis of genetically mutated cells with AFM reveal abnormalities of the cytoskeleton, cell membrane structures, and defects of contractility. The higher the Young's modulus, the stiffer the cell, and it is well known that abnormal tissue stiffness is symptomatic of a range of diseases. The cell beating force and frequency provide information during the depolarization and repolarization phases, complementary to cell electrophysiology (calcium imaging, MEA, patch clamp). In addition, original data is also presented to emphasize the unique potential of AFM as a tool to assess fibrosis in cardiac tissue.

摘要

致心律失常性右室心肌病(ACM)是一种遗传性心肌疾病,其特征为心肌细胞逐渐被纤维脂肪组织取代、心室扩张、心功能障碍、心律失常和心源性猝死。人们对这些疾病的分子生物力学越来越感兴趣。原子力显微镜(AFM)是一种成熟的技术,可在细胞尺度上研究生理和病理条件下生物样本的机械生物学。然而,仍然缺乏一篇综述来描述使用 AFM 可以获得的所有不同数据(细胞弹性、粘附行为、粘弹性、搏动力和频率)。在这篇综述中,我们将讨论几种技术,这些技术突出了 AFM 作为评估 ACM 中涉及的生物力学的工具的潜力。实际上,使用 AFM 分析遗传突变细胞显示细胞骨架、细胞膜结构异常和收缩缺陷。杨氏模量越高,细胞越硬,众所周知,异常组织硬度是多种疾病的症状。细胞搏动力和频率在去极化和复极化阶段提供信息,与细胞电生理学(钙成像、MEA、膜片钳)互补。此外,还呈现了原始数据,以强调 AFM 作为评估心脏组织纤维化的工具的独特潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0184/8998711/83b50fc29b7f/ijms-23-03700-g001.jpg

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