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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2021, Vol. 15 Issue (1) : 43-52    https://doi.org/10.1007/s11684-020-0769-6
REVIEW
Applications of atomic force microscopy in immunology
Jiping Li1, Yuying Liu2,3, Yidong Yuan1,4, Bo Huang2,3,5()
1. Beijing Smartchip Microelectronics Technology Company Limited, Beijing 100192, China
2. Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China
3. Clinical Immunology Center, Chinese Academy of Medical Sciences, Beijing 100005, China
4. School of Microelectronics, Tianjin University, Tianjin 300072, China
5. Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China
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Abstract

Cellular mechanics, a major regulating factor of cellular architecture and biological functions, responds to intrinsic stresses and extrinsic forces exerted by other cells and the extracellular matrix in the microenvironment. Cellular mechanics also acts as a fundamental mediator in complicated immune responses, such as cell migration, immune cell activation, and pathogen clearance. The principle of atomic force microscopy (AFM) and its three running modes are introduced for the mechanical characterization of living cells. The peak force tapping mode provides the most delicate and desirable virtues to collect high-resolution images of morphology and force curves. For a concrete description of AFM capabilities, three AFM applications are discussed. These applications include the dynamic progress of a neutrophil-extracellular-trap release by neutrophils, the immunological functions of macrophages, and the membrane pore formation mediated by perforin, streptolysin O, gasdermin D, or membrane attack complex.

Keywords cellular mechanics      atomic force microscopy      neutrophil extracellular trap      macrophage phagocytosis      pore formation     
Corresponding Author(s): Bo Huang   
Just Accepted Date: 10 July 2020   Online First Date: 19 August 2020    Issue Date: 11 February 2021
 Cite this article:   
Jiping Li,Yuying Liu,Yidong Yuan, et al. Applications of atomic force microscopy in immunology[J]. Front. Med., 2021, 15(1): 43-52.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-020-0769-6
https://academic.hep.com.cn/fmd/EN/Y2021/V15/I1/43
Fig.1  Basic atomic force microscope (AFM) setup: a cantilever probe, a piezoelectric actuator (not drawn), a laser source, and a position-sensitive detector.
Fig.2  Force–distance curve by AFM. In one measurement cycle, the probe approaches the sample to make a tip–sample contact and then retracts for a complete graph of tip force interactions, where Young’s modulus (by the linear slope), membrane deformation (by the maximum indentation), adhesion force (by the maximum adhesion point), and energy dissipation (by the enclosed area) can be extracted.
Fig.3  NETosis process and entropic swelling of chromatin. The process can be divided into three distinct phases with no return in accordance with the chromatin status.
Fig.4  SLO/perforin-mediated membrane pore formation. (A) Principle of perforin-induced pore formation and cell death. (B) Surface roughness and topography measurements of OVA-B16 cells treated with PBS, perforin (50 U), and streplysin O (SLO) (50 U) isolated from activated human CD8+ T cells for 5 min. The white line across the pore image on the SLO-treated cell indicates the location for topography measurements on the right. The pore depth is defined as the vertical distance between the two red horizontal lines on the curve diagram, and the pore diameter is defined as the horizontal distance between the two dotted blue vertical lines. This result is from Liu et al. (Cell Mol Immunol. 2019;16:611. Open Access.)
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