Application of AFM to the Nanomechanics of Cancer

MRS Advances ◽  
2016 ◽  
Vol 1 (25) ◽  
pp. 1817-1827 ◽  
Author(s):  
Shivani Sharma ◽  
James K Gimzewski

ABSTRACTCancer cell metastasis is a leading cause of mortality whereby cancer cells migrate from a tumor and spread to distant sites in the body. Understanding metastasis requires a deeper understanding of biomechanics and mechanobiology at the cellular level. We have established the use of Atomic Force Microscopy to infer the mechanical properties of single cells in cultures by measurement of their Young’s modulus. Here we discuss the main advantages, challenges, technological limitations and applicability of AFM based cell mechanics studies along with other emerging high throughput techniques for the development of single cell mechanical based clinical assays for cancer detection and management.

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuri M. Efremov ◽  
Svetlana L. Kotova ◽  
Anastasia A. Akovantseva ◽  
Peter S. Timashev

Abstract Background The nucleus, besides its functions in the gene maintenance and regulation, plays a significant role in the cell mechanosensitivity and mechanotransduction. It is the largest cellular organelle that is often considered as the stiffest cell part as well. Interestingly, the previous studies have revealed that the nucleus might be dispensable for some of the cell properties, like polarization and 1D and 2D migration. Here, we studied how the nanomechanical properties of cells, as measured using nanomechanical mapping by atomic force microscopy (AFM), were affected by the removal of the nucleus. Methods The mass enucleation procedure was employed to obtain cytoplasts (enucleated cells) and nucleoplasts (nuclei surrounded by plasma membrane) of two cell lines, REF52 fibroblasts and HT1080 fibrosarcoma cells. High-resolution viscoelastic mapping by AFM was performed to compare the mechanical properties of normal cells, cytoplasts, and nucleoplast. The absence or presence of the nucleus was confirmed with fluorescence microscopy, and the actin cytoskeleton structure was assessed with confocal microscopy. Results Surprisingly, we did not find the softening of cytoplasts relative to normal cells, and even some degree of stiffening was discovered. Nucleoplasts, as well as the nuclei isolated from cells using a detergent, were substantially softer than both the cytoplasts and normal cells. Conclusions The cell can maintain its mechanical properties without the nucleus. Together, the obtained data indicate the dominating role of the actomyosin cytoskeleton over the nucleus in the cell mechanics at small deformations inflicted by AFM.


2015 ◽  
Vol 12 (104) ◽  
pp. 20140970 ◽  
Author(s):  
Kristina Haase ◽  
Andrew E. Pelling

Transmission of mechanical force is crucial for normal cell development and functioning. However, the process of mechanotransduction cannot be studied in isolation from cell mechanics. Thus, in order to understand how cells ‘feel’, we must first understand how they deform and recover from physical perturbations. Owing to its versatility, atomic force microscopy (AFM) has become a popular tool to study intrinsic cellular mechanical properties. Used to directly manipulate and examine whole and subcellular reactions, AFM allows for top-down and reconstitutive approaches to mechanical characterization. These studies show that the responses of cells and their components are complex, and largely depend on the magnitude and time scale of loading. In this review, we generally describe the mechanotransductive process through discussion of well-known mechanosensors. We then focus on discussion of recent examples where AFM is used to specifically probe the elastic and inelastic responses of single cells undergoing deformation. We present a brief overview of classical and current models often used to characterize observed cellular phenomena in response to force. Both simple mechanistic models and complex nonlinear models have been used to describe the observed cellular behaviours, however a unifying description of cell mechanics has not yet been resolved.


2014 ◽  
Vol 28 (7) ◽  
pp. 449-455 ◽  
Author(s):  
Ryosuke Takahashi ◽  
Satoshi Ichikawa ◽  
Agus Subagyo ◽  
Kazuhisa Sueoka ◽  
Takaharu Okajima

Author(s):  
Haijiao Liu ◽  
Craig A. Simmons ◽  
Yu Sun

Mechanical stimuli, including the elasticity of the extracellular matrix (ECM), can have profound effects on the function of cells and their responsiveness to other microenvironmental cues, thereby regulating homeostasis and disease development. For example, the response of aortic valve interstitial cells (VICs) to growth factors [1] and VIC differentiation to pathological phenotypes [2] depend on ECM elasticity. The ability of cells to sense and respond to mechanical stimuli depends on several factors, including their inherent cellular-level mechanical properties. The mechanical properties of suspended VICs [3, 4] and VICs grown on stiff glass/polystyrene [5] have been reported. However, neither of these test conditions is physiological, as VICs adhere to ECM that is orders of magnitude more compliant than glass. Some other cell types adapt their stiffness to that of their substrate [6]; we hypothesized that adherent VICs would similarly change their elasticity in response to the elastic properties of their ECM.


Nanoscale ◽  
2019 ◽  
Vol 11 (18) ◽  
pp. 8918-8929 ◽  
Author(s):  
Enrique A. López-Guerra ◽  
Hongchen Shen ◽  
Santiago D. Solares ◽  
Danmeng Shuai

History-dependent viscoelastic analysis by atomic force microscopy delivers highly spatial-localized biofilm properties within a wide time–frequency window.


Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 219
Author(s):  
Agnieszka Kurek ◽  
Estera Kłosowicz ◽  
Kamila Sofińska ◽  
Robert Jach ◽  
Jakub Barbasz

The endometrium lines the uterine cavity, enables implantation of the embryo, and provides an environment for its development and growth. Numerous methods, including microscopic and immunoenzymatic techniques, have been used to study the properties of the cells and tissue of the endometrium to understand changes during, e.g., the menstrual cycle or implantation. Taking into account the existing state of knowledge on the endometrium and the research carried out using other tissues, it can be concluded that the mechanical properties of the tissue and its cells are crucial for their proper functioning. This review intends to emphasize the potential of atomic force microscopy (AFM) in the research of endometrium properties. AFM enables imaging of tissues or single cells, roughness analysis, and determination of the mechanical properties (Young’s modulus) of single cells or tissues, or their adhesion. AFM has been previously shown to be useful to derive force maps. Combining the information regarding cell mechanics with the alternations of cell morphology or gene/protein expression provides deeper insight into the uterine pathology. The determination of the elastic modulus of cells in pathological states, such as cancer, has been proved to be useful in diagnostics.


Author(s):  
Julie X. Yun ◽  
Lixia Zhang ◽  
Delphine Dean ◽  
Martine LaBerge ◽  
Hai Yao

The temporomandibular joint (TMJ) is a load bearing joint with unique articular structure. The TMJ disc, a fibrocartilaginous tissue, is a major component of jaw function by serving stress distribution and lubrication in the joint. The TMJ disc pathophysiology, such as disc derangement and degeneration, is central to many TMJ disorders affecting a large population. It is generally believed that pathological mechanical loading, such as sustained mechanical loading in jaw clenching and traumatic impact, is the leading cause of TMJ disc derangement [1]. However, the exact mechanism, especially at the cellular level, has not been established. TMJ disc cells, fibrochondrocyte-like cells, respond to chemical and mechanical signals and regulate the physiology and pathology of the disc. However, little is known of the cellular mechanical properties in TMJ disc. The objective of this study is to determine the mechanical properties of a single TMJ disc cell using atomic force microscopy (AFM).


2000 ◽  
Vol 39 (Part 1, No. 6B) ◽  
pp. 3711-3716 ◽  
Author(s):  
Hatsuki Shiga ◽  
Yukako Yamane ◽  
Etsuro Ito ◽  
Kazuhiro Abe ◽  
Kazushige Kawabata ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Richard J. Smith ◽  
Fernando Pérez-Cota ◽  
Leonel Marques ◽  
Matt Clark

AbstractBrillouin light scattering (BLS) is an emerging method for cell imaging and characterisation. It allows elasticity-related contrast, optical resolution and label-free operation. Phonon microscopy detects BLS from laser generated coherent phonon fields to offer an attractive route for imaging since, at GHz frequencies, the phonon wavelength is sub-optical. Using phonon fields to image single cells is challenging as the signal to noise ratio and acquisition time are often poor. However, recent advances in the instrumentation have enabled imaging of fixed and living cells. This work presents the first experimental characterisation of phonon-based axial resolution provided by the response to a sharp edge. The obtained axial resolution is up to 10 times higher than that of the optical system used to take the measurements. Validation of the results are obtained with various polymer objects, which are in good agreement with those obtained using atomic force microscopy. Edge localisation, and hence profilometry, of a phantom boundary is measured with accuracy and precision of approximately 60 nm and 100 nm respectively. Finally, 3D imaging of fixed cells in culture medium is demonstrated.


Coatings ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 652
Author(s):  
Divine Sebastian ◽  
Chun-Wei Yao ◽  
Lutfun Nipa ◽  
Ian Lian ◽  
Gary Twu

In this work, a mechanically durable anticorrosion superhydrophobic coating is developed using a nanocomposite coating solution composed of silica nanoparticles and epoxy resin. The nanocomposite coating developed was tested for its superhydrophobic behavior using goniometry; surface morphology using scanning electron microscopy and atomic force microscopy; elemental composition using energy dispersive X-ray spectroscopy; corrosion resistance using atomic force microscopy; and potentiodynamic polarization measurements. The nanocomposite coating possesses hierarchical micro/nanostructures, according to the scanning electron microscopy images, and the presence of such structures was further confirmed by the atomic force microscopy images. The developed nanocomposite coating was found to be highly superhydrophobic as well as corrosion resistant, according to the results from static contact angle measurement and potentiodynamic polarization measurement, respectively. The abrasion resistance and mechanical durability of the nanocomposite coating were studied by abrasion tests, and the mechanical properties such as reduced modulus and Berkovich hardness were evaluated with the aid of nanoindentation tests.


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