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Published on: February 22, 2018
Atomic Force Microscopy (AFM) Applications in Arrhythmogenic Cardiomyopathy
Brisa Peña1,2,3, Mostafa Adbel-Hafiz2, Maria Cavasin3,4
1CU-Cardiovascular Institute, University of Colorado Anschutz Medical Campus, 12700 East 19th Ave., Aurora, CO 80045, USA.
Insights
Atomic force microscopy (AFM) reveals cellular biomechanical changes in arrhythmogenic cardiomyopathy (ACM). This technique assesses cell elasticity, contractility, and fibrosis, offering new insights into this inherited heart muscle disorder.
Area of Science:
- Cardiovascular Research
- Biophysics
- Cellular Mechanobiology
Background:
- Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder.
- Fibrofatty tissue replacement of cardiomyocytes leads to ventricular dysfunction and sudden cardiac death.
- Molecular biomechanics is crucial for understanding ACM pathogenesis.
Purpose of the Study:
- To review the application of Atomic Force Microscopy (AFM) in assessing cardiac biomechanics in ACM.
- To highlight the diverse data obtainable from AFM, including cell elasticity, adhesion, viscoelasticity, and contractility.
- To emphasize AFM's potential for evaluating fibrosis in cardiac tissue.
Main Methods:
- Utilizing Atomic Force Microscopy (AFM) to probe cellular biomechanical properties.
- Analyzing genetically mutated cells to identify cytoskeletal and membrane abnormalities.
- Measuring cell elasticity (Young's modulus), beating force, and frequency.
- Assessing tissue fibrosis using AFM.
Main Results:
- AFM analysis of mutated cells reveals cytoskeleton and cell membrane abnormalities.
- Increased cell stiffness (Young's modulus) is indicative of pathological changes.
- AFM provides complementary data to electrophysiology, including cell beating force and frequency.
- Original data demonstrates AFM's capability in assessing cardiac tissue fibrosis.
Conclusions:
- AFM is a powerful tool for characterizing the biomechanical alterations in arrhythmogenic cardiomyopathy.
- AFM offers insights into cellular dysfunction, contractility defects, and tissue fibrosis in ACM.
- This technique enhances our understanding of ACM mechanobiology and aids in disease assessment.
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.
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