Sub-cellular force microscopy in single normal and cancer cells

Babahosseini, Hesam; Carmichael, Ben; Strobl, Jeannine S.; Mahmoodi, S. Nima; Agah, Masoud

doi:10.1016/j.bbrc.2015.05.100

Cited by 33 publications

(36 citation statements)

References 32 publications

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“…Generalized Maxwell model with two or more relaxation times increased the quality of the fit relative to the single relaxation time like in SLS model 44, 47, 50 . But it is not completely clear if it is really capturing some physical phenomena or quality of the fit increased just due to the introduction of additional fitting parameters.…”

Section: Discussionmentioning

confidence: 99%

Measuring nanoscale viscoelastic parameters of cells directly from AFM force-displacement curves

Efremov

Wang

Hardy

et al. 2017

Sci Rep

217

184

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Force-displacement (F-ZIn recent years interest has increased in the measurement of the viscoelastic properties of soft biological samples motivated by their correlation with disease, differentiation, or cellular transformation [1][2][3][4] . A large variety of methods have been introduced for measuring cellular mechanical properties including micropipette aspiration 5,6 , stretching or compression between two microplates [7][8][9] , optical tweezers 10,11 , and magnetic twisting cytometry 12,13 . However, indentation with the atomic force microscope (AFM) remains one of the most popular methods for probing the nanoscale properties of soft samples like cells, tissues and hydrogels [14][15][16][17] . In the AFM, the elastic properties of live cells are usually evaluated from force versus displacement (F-Z) curves. Then the Hertz model or its modifications are applied to the approach part of the F-Z curve to extract Young's modulus (E Hertz ), the elastic parameter used for characterization of the sample's mechanical properties 18,19 . However, such models assume a purely elastic nature of the sample, while in reality most biological samples are viscoelastic. Viscoelasticity is revealed in a clear hysteresis between the approach and retraction parts of curves 20 ; the indentation speed dependence of E Hertz values extracted from force curves with the Hertz model 11 ; the observations of force relaxation at constant indentation depth and the creep at constant loading force 21 . Approaches other than the standard F-Z curves are usually used to obtain the viscoelastic properties of samples with AFM in both the time [22][23][24] and frequency domains [25][26][27][28][29][30] . These generally require modifications in the AFM apparatus and/or in the data acquisition protocol. Equally importantly, each approach has its own sets of measurement uncertainties.If a standard F-Z curve could also be used to quantify viscoelastic properties, it would allow one standard method with well quantified uncertainties 31 to be used for both viscoelasticity and elasticity measurements. This has not been possible to date, we believe, due to the lack of a mathematical/computational framework that allows the post-processing of force-displacement data to extract the relevant viscoelastic constitutive parameters.

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Section: Discussionmentioning

confidence: 99%

Measuring nanoscale viscoelastic parameters of cells directly from AFM force-displacement curves

Efremov

Wang

Hardy

et al. 2017

Sci Rep

217

184

View full text Add to dashboard Cite

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“…These velocity profiles vary between normal cells and cancer cells, because cancer cells have lower membrane stiffness and cytoskeleton strength as documented by previous studies. 3,4,40,41 The velocity of the cells depends on fluidic pressure, flow rate, and the geometry of the cells. The cross-section of the microfluidic channels and flow rate are kept constant for both MDA-MB-231 and MCF-10A medium, so that the Reynolds number of both samples can be considered constant.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Mechanical Characteristics Analyzed by Multiconstriction Microfluidic Channels

et al. 2017

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A microfluidic device composed of variable numbers of multiconstriction channels is reported in this paper to differentiate a human breast cancer cell line, MDA-MB-231, and a nontumorigenic human breast cell line, MCF-10A. Differences between their mechanical properties were assessed by comparing the effect of single or multiple relaxations on their velocity profiles which is a novel measure of their deformation ability. Videos of the cells were recorded via a microscope using a smartphone, and imported to a tracking software to gain the position information on the cells. Our results indicated that a multiconstriction channel design with five deformation (50 μm in length, 10 μm in width, and 8 μm in height) separated by four relaxation (50 μm in length, 40 μm in width, and 30 μm in height) regions was superior to a single deformation design in differentiating MDA-MB-231 and MCF-10A cells. Velocity profile criteria can achieve a differentiation accuracy around 95% for both MDA-MB-231 and MCF-10A cells.

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“…Besides Young's modulus, studies have shown that the relaxation time [134] and cell adhesion [135], [152] of cancer cells are also different from normal cells. In 2012, Bastatas et al [163] investigated the mechanics and calcium dynamics of prostate cancer cells with distinct metastatic potential.…”

Section: Discussion and Perspectivementioning

confidence: 99%

“…5) involve the physical processes of the cancer cells, such as adhesion and deformation [129]. The cancer cells with low stiffness are more deformable than their normal counterparts which are with high stiffness [13], [134]. A recent study by Smolyakov et al [135] has utilized AFM to compare the stiffness and adhesion between breast cancer cells with different metastatic potentials.…”

Section: Mechanical Dynamics Of Cells In Cancermentioning

confidence: 99%

Atomic Force Microscopy in Characterizing Cell Mechanics for Biomedical Applications: A Review

Dang

Liu

et al. 2017

IEEE Trans.on Nanobioscience

104

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-Cell mechanics is a novel label-free biomarker for indicating cell states and pathological changes. The advent of atomic force microscopy (AFM) provides a powerful tool for quantifying the mechanical properties of single living cells in aqueous conditions. The wide use of AFM in characterizing cell mechanics in the past two decades has yielded remarkable novel insights in understanding the development and progression of certain diseases, such as cancer, showing the huge potential of cell mechanics for practical applications in the field of biomedicine. In this paper, we reviewed the utilization of AFM to characterize cell mechanics. First, the principle and method of AFM single-cell mechanical analysis was presented, along with the mechanical responses of cells to representative external stimuli measured by AFM. Next, the unique changes of cell mechanics in two types of physiological processes (stem cell differentiation, cancer metastasis) revealed by AFM were summarized. After that, the molecular mechanisms guiding cell mechanics were analyzed. Finally the challenges and future directions were discussed.

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Sub-cellular force microscopy in single normal and cancer cells

Cited by 33 publications

References 32 publications

Measuring nanoscale viscoelastic parameters of cells directly from AFM force-displacement curves

Measuring nanoscale viscoelastic parameters of cells directly from AFM force-displacement curves

Single-Cell Mechanical Characteristics Analyzed by Multiconstriction Microfluidic Channels

Atomic Force Microscopy in Characterizing Cell Mechanics for Biomedical Applications: A Review

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