Applicability of atomic force microscopy to determine cancer-related changes in cells

Abstract

The determination of mechanical properties of living cells as an indicator of cancer progression has become possible with the development of local measurement techniques such as atomic force microscopy (AFM). Its most important advantage is a nanoscopic character, implying that very local alterations can be quantified. The results gathered from AFM measurements of various cancers show that, for most cancers, individual cells are characterized by the lower apparent Young's modulus, denoting higher cell deformability. The measured value depends on various factors, like the properties of substrates used for cell growth, force loading rate or indentation depth. Despite this, the results proved the AFM capability to recognize mechanically altered cells. This can significantly impact the development of methodological approaches toward the precise identification of pathological cells. This article is part of the theme issue ‘Nanocracks in nature and industry’.

Harnessing atomic force microscopy‐based single‐cell analysis to advance physical oncology

“…Nevertheless, our current understanding of how There is still much room for the studies of applying AFM-based single-cell analysis toolbox to detect the mechanical behaviors of single cancer cells. Current studies of utilizing AFM to measure cellular mechanical properties mainly focus on measuring a single mechanical property of cancer cells, such as cell elasticity (Cross et al, 2007;Gavara & Chadwick, 2012;Lekka, 2022;Perez-Dominguez et al, 2020;Plodinec et al, 2012;Prasad et al, 2021). However, the mechanical properties of cells are highly complex, which include not only elasticity but also viscosity, poroelasticity, plasticity and nonlinear elasticity, and are time-and frequency-dependent (Chaudhuri et al, 2020).…”

“…AFM has become an important and multifunctional toolbox for singlecell analysis (Figure 1) which is widely utilized in the studies of exploring mechanics in tumors at the micro/nanoscale (Kwon et al, 2019;Lekka, 2022;Li, Xi, Wang, & Liu, 2021;Yu et al, 2017)…”

“…Among these technologies, AFM is a powerful and unique one (Garcia, 2020; Krieg et al, 2019) which is able to not only visualize the diverse fine structures of living cells, but also quantify and map multiple mechanical properties of the cells. AFM has become an important and multifunctional toolbox for single‐cell analysis (Figure 1) which is widely utilized in the studies of exploring mechanics in tumors at the micro/nanoscale (Kwon et al, 2019; Lekka, 2022; Li et al, 2019; Li, Xi, Wang, & Liu, 2021; Yu et al, 2017), providing numerous novel insights into the mechanical cues involved in tumor behaviors that are inaccessible by other methods and contributing much to the field of cancer mechanobiology. Herein, the achievements of AFM‐based single‐cell analysis in the studies of uncovering the underlying mechanics of cancer cells in tumor formation and progression are summarized and illustrated in detail from three aspects, including topographical imaging, mechanical measurement, and interactions between cancer cells and tumor microenvironment, and the challenges as well as future perspectives of AFM‐based single‐cell analysis for physical oncology are discussed.…”

Self-assembled peptide nanoparticles for photodynamic therapy: morphological and mechanical effects on hepatocellular carcinoma cells

“…In recent years, cell mechanics has been recognized as a novel label-free biomarker for indicating cell states and pathological changes, and much effort has gone into this field for its practical application in biomedicine. The advent of various new technologies, especially atomic force microscopy (AFM), have enabled the measurement of biophysical properties, including cell stiffness, viscoelasticity, deformability, morphology, topography, and adhesion [39][40][41], which can serve as a marker for cellular phenotypic events, establishing a better understanding of tumor behaviors, defining the stage of cancer progression as a promising biomarker for cancer diagnosis and prognosis, and even helping to overcome cancer therapy resistance [42][43][44]. Despite some achievements, for example, cell membrane roughness of single colon cancer cells has been analyzed during apoptosis in PDT [45], other essential biophysical aspects, such as morphology and stiffness, and in particular the effects of peptide-based nanoparticles on the biophysical properties of cancer cells, have not been adequately studied.…”

Nanocracks in nature and industry

“…The first paper in this volume [ 19 ] describes experiments and theory that add to the original JKR concept by considering very small contacts in which the circular crack has nano-dimensions. This is followed by three papers [ 20 – 22 ] that investigate such JKR nanocracks in various circumstances, including adhesion of biofilm cells, elastic properties of cancer cells and the influence of shear forces that change the behaviour of the JKR cracks as sliding begins to occur. These papers focus on small-diameter contacts through which nanocracks propagate.…”