Interrogation of drug effects on HeLa cells by exploiting new AFM mechanical biomarkers

Yun, Xiaoling; Tang, Mingjie; Yang, Zhongbo; Wilksch, Jonathan J.; Xiu, Peng; Gao, Haiyang; Zhang, Feng; Wang, Huabin

doi:10.1039/c7ra06233h

Cited by 32 publications

(61 citation statements)

References 40 publications

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“… 8 , 27 However, the cells treated with AgNPs present clear alterations in both morphology and number ( Figure 1 B,C), i.e., the cells tended to turn into a roundish shape and the cell density gradually decreased with increasing concentration of AgNPs, similar to the effect of graphene oxide sheets on HEK293T cells and other drugs or NPs on HeLa cells and/or MDA-MB-231 cells. 8 , 18 , 28 The morphological and inhibitory changes indicated that AgNPs are cytotoxic to HEK293T cells.…”

Section: Results and Discussionmentioning

confidence: 99%

“…Previous studies have suggested that the factor of viscosity is a much more meaningful physical parameter than the usually used Young’s modulus obtained by the Hertz–Sneddon model because cells are viscoelastic materials and, strictly speaking, cannot be modeled as an ideal elastic body using the Hertz–Sneddon model. 18 …”

Section: Results and Discussionmentioning

confidence: 99%

“… 20 More recently, we used the factor of viscosity to evaluate the action of an anticancer drug (docetaxol) on HeLa cells and found that docetaxol-treated cells had a smaller factor of viscosity than the untreated cells. 18 These studies demonstrated that the mechanical properties of cells are very sensitive to the cell state/functional change, strongly implicating that the influence of NPs on cells could be examined using AFM-based mechanical measurements. Compared to those fluorescence-based techniques, the AFM-based biomechanical techniques are label-free and can assess the cell state from the perspective of mechanics.…”

Section: Introductionmentioning

confidence: 94%

See 2 more Smart Citations

Nanotoxicity of Silver Nanoparticles on HEK293T Cells: A Combined Study Using Biomechanical and Biological Techniques

Jiang

Tang

et al. 2018

ACS Omega

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Human embryonic kidney 293T cells (HEK293T cells) before and after treatment with silver nanoparticles (AgNPs) were measured using advanced atomic force microscopy (AFM) force measurement technique, and the biomechanical property of cells was analyzed using a theoretical model. The biomechanical results showed that the factor of viscosity of untreated HEK293T cells reduced from 0.65 to 0.40 for cells exposure to 40 μg/mL of AgNPs. Comet assay indicated that significant DNA damage occurred in the treated cells, measured as tail DNA% and tail moment. Furthermore, gene expression analysis showed that for the cells treated with 40 μg/mL of AgNPs, the antiapoptosis genes Bcl2-t and Bclw were, respectively, downregulated to 0.65- and 0.66-fold of control, and that the proapoptosis gene Bid was upregulated to 1.55-fold of control, which indicates that apoptosis occurred in cells exposed to AgNPs. Interestingly, excellent negative correlations were found between the factor of viscosity and tail DNA%, and tail moment, which suggest that the biomechanical property can be correlated with genotoxicity of nanoparticles on the cells. Based on the above results, we conclude that (1) AgNPs can lead to biomechanical changes in HEK293T cells, concomitantly with biological changes including cell viability, DNA damage, and cell apoptosis; (2) the factor of viscosity can be exploited as a promising label-free biomechanical marker to assess the nanotoxicity of nanoparticles on the cells; and (3) the combination of AFM-based mechanical technique with conventional biological methods can provide more comprehensive understanding of the nanotoxicity of nanoparticles than merely by using the biological techniques.

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Section: Results and Discussionmentioning

confidence: 99%

Section: Results and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

See 1 more Smart Citation

Nanotoxicity of Silver Nanoparticles on HEK293T Cells: A Combined Study Using Biomechanical and Biological Techniques

Jiang

Tang

et al. 2018

ACS Omega

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“…The depth of the OTSpd chemical pattern provides a height reference for calculating the thickness of other parallel layer on itself. Although some studies applied AFM cross-section profile to analyze the height of object [ 28 – 30 ], it is believed that AFM topography histogram can better represent the average height change of pattern areas in the present work due to the protein film, which is immobilized on the chemical patterns, exhibiting an “unflat” surface. Histograms of the corresponding heights were fitted to two Gaussian functions by using MicroCal Origin software in order to enable a quantitative comparison.…”

Section: Methodsmentioning

confidence: 99%

Investigating and characterizing the binding activity of the immobilized calmodulin to calmodulin-dependent protein kinase I binding domain with atomic force microscopy

Zhang

2017

Chemistry Central Journal

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Protein–protein interactions are responsible for many biological processes, and the study of how proteins undergo a conformational change induced by other proteins in the immobilized state can help us to understand a protein’s function and behavior, empower the current knowledge on molecular etiology of disease, as well as the discovery of putative protein targets of therapeutic interest. In this study, a bottom-up approach was utilized to fabricate micro/nanometer-scale protein patterns. One cysteine mutated calmodulin (CaM), as a model protein, was immobilized on thiol-terminated pattern surfaces. Atomic Force Microscopy (AFM) was then employed as a tool to investigate the interactions between CaM and CaM kinase I binding domain, and show that the immobilized CaM retains its activity to interact with its target protein. Our work demonstrate the potential of employing AFM to the research and assay works evolving surface-based protein–protein interactions biosensors, bioelectronics or drug screening.Electronic supplementary materialThe online version of this article (10.1186/s13065-017-0360-7) contains supplementary material, which is available to authorized users.

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“…As this method evolves over time, researchers have recognized the importance of integrating OEK with other devices/ tools to detect, analyze, and measure micro/nano-objects for biomedical and tissue engineering applications. This requires systematically combining OEK chips with other predominant micro/ nanorobotic-based techniques, such as atomic force microscopy, 119 acoustics tweezers, 120 and scanning ion conductance microscopy, 121 to achieve efficient 3D manipulation and multiparameter simultaneous acquisition, detection, and analysis of single cells.…”

Section: Challenges and Prospectsmentioning

confidence: 99%

Optoelectrokinetics-based microfluidic platform for bioapplications: A review of recent advances

et al. 2019

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The introduction of optoelectrokinetics (OEK) into lab-on-a-chip systems has facilitated a new cutting-edge technique-the OEK-based micro/nanoscale manipulation, separation, and assembly processes-for the microfluidics community. This technique offers a variety of extraordinary advantages such as programmability, flexibility, high biocompatibility, low-cost mass production, ultralow optical power requirement, reconfigurability, rapidness, and ease of integration with other microfluidic units. This paper reviews the physical mechanisms that govern the manipulation of micro/nano-objects in microfluidic environments as well as applications related to OEK-based micro/nanoscale manipulation-applications that span from single-cell manipulation to single-molecular behavior determination. This paper wraps up with a discussion of the current challenges and future prospects for the OEK-based microfluidics technique. The conclusion is that this technique will allow more opportunities for biomedical and bioengineering researchers to improve lab-on-a-chip technologies and will have farreaching implications for biorelated researches and applications in the future.

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Interrogation of drug effects on HeLa cells by exploiting new AFM mechanical biomarkers

Abstract: New AFM mechanical biomarkers including cell brush length, adhesion work and the factor of viscosity are discovered for drug assays.

Cited by 32 publications

References 40 publications

Nanotoxicity of Silver Nanoparticles on HEK293T Cells: A Combined Study Using Biomechanical and Biological Techniques

Nanotoxicity of Silver Nanoparticles on HEK293T Cells: A Combined Study Using Biomechanical and Biological Techniques

Investigating and characterizing the binding activity of the immobilized calmodulin to calmodulin-dependent protein kinase I binding domain with atomic force microscopy

Optoelectrokinetics-based microfluidic platform for bioapplications: A review of recent advances

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