Single-cell mechanics – An experimental–computational method for quantifying the membrane–cytoskeleton elasticity of cells

Tartibi, Mehrzad; Liu, Y. X.; Liu, Gang-yu; Komvopoulos, K.

doi:10.1016/j.actbio.2015.08.028

Cited by 14 publications

(9 citation statements)

References 28 publications

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“…This nanomechanical phenotype is a complex result of the unique properties of cell membrane, underlying cytoskeleton and cell turgor, which together reflect an epithelial-mesenchymal transition for promoting cell mobility (34). Nanomechanical parameters, most notably elasticity and adhesion, have been proposed to provide a rich resource for robust characterization of human cells, including distinguishing between cancer and normal cells, and also for fine stratification of cancer cells according to their malignancy (35,36).…”

Section: Discussionmentioning

confidence: 99%

EpCAM-Regulated Transcription Exerts Influences on Nanomechanical Properties of Endometrial Cancer Cells That Promote Epithelial-to-Mesenchymal Transition

et al. 2016

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Overexpression of epithelial cell adhesion molecule (EpCAM) has been implicated in advanced endometrial cancer, but its roles in this progression remain to be elucidated. In addition to its structural role in modulating cell-surface adhesion, here we demonstrate that EpCAM is a regulatory molecule in which its internalization into the nucleus turns on a transcription program. Activation of EGF/EGFR signal transduction triggered cell-surface cleavage of EpCAM, leading to nuclear internalization of its cytoplasmic domain EpICD. ChIP-seq analysis identified target genes that are co-regulated by EpICD and its transcription partner, LEF-1. Network enrichment analysis further uncovered a group of 105 genes encoding functions for tight junction, adherent and cell migration. Furthermore, nanomechanical analysis by atomic force microscope (AFM) revealed increased softness and decreased adhesiveness of EGF-stimulated cancer cells, implicating acquisition of an epithelial-mesenchymal transition (EMT) phenotype. Thus, genome editing of EpCAM could be associated with altering these nanomechanical properties towards a less aggressive phenotype. Using this integrative genomic-biophysical approach, we demonstrate for the first time an intricate relationship between EpCAM-regulated transcription and altered biophysical properties of cells that promote EMT in advanced endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

EpCAM-Regulated Transcription Exerts Influences on Nanomechanical Properties of Endometrial Cancer Cells That Promote Epithelial-to-Mesenchymal Transition

et al. 2016

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“…Two-dimensional platforms can be easily combined with techniques such as atomic force microscopy (AFM) (as an example) to not only measure the mechanical properties of migrating cells but also assess the cellular response to cellular and matrix deformations that are created using the AFM cantilever [93]. In metastasis research, AFM has been utilized in conjunction with 2D models of migration to study the mechanical properties of migrating cells by investigating and characterizing alterations to the cytoskeleton and ECM [94][95][96][97][98]. Such studies have demonstrated that the cytoskeleton of metastatic cells responds to mechanical loads differently than that of a nonmetastatic cell, as these cells are typically more compliant [99,100].…”

Section: Two-dimensional Versus 3d Metastatic Movementmentioning

confidence: 99%

The Mechanics of Single Cell and Collective Migration of Tumor Cells

Lintz

Muñoz

Reinhart‐King

2017

Journal of Biomechanical Engineering

123

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Metastasis is a dynamic process in which cancer cells navigate the tumor microenvironment, largely guided by external chemical and mechanical cues. Our current understanding of metastatic cell migration has relied primarily on studies of single cell migration, most of which have been performed using two-dimensional (2D) cell culture techniques and, more recently, using three-dimensional (3D) scaffolds. However, the current paradigm focused on single cell movements is shifting toward the idea that collective migration is likely one of the primary modes of migration during metastasis of many solid tumors. Not surprisingly, the mechanics of collective migration differ significantly from single cell movements. As such, techniques must be developed that enable in-depth analysis of collective migration, and those for examining single cell migration should be adopted and modified to study collective migration to allow for accurate comparison of the two. In this review, we will describe engineering approaches for studying metastatic migration, both single cell and collective, and how these approaches have yielded significant insight into the mechanics governing each process.

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“…Conventional techniques such as micropipette aspiration 21 , optical tweezer 22 , and atomic force microscopy (AFM) 23,24 apply localized forces to single cells to characterize cellular mechanical properties. However, these techniques are generally not amenable for assessing an ensemble of cells simultaneously.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, AFM has been utilized to assess mechanical property of cells 24,32 including macrophages 20,33,34 . Used as an indentation method via the compression of cantilever onto the cell membrane and measurement of ensuing deformation of the cell surface, Young’s modulus of macrophages were obtained to be in a wide range of values 20,33,34 , from 0.8 kPa up to 60 kPa, depending on factors such as surface coating and incubation time.…”

Section: Discussionmentioning

confidence: 99%

Acoustic tweezing cytometry for mechanical phenotyping of macrophages and mechanopharmaceutical cytotripsy

Hong

Rzeczycki

Keswani

et al. 2019

Sci Rep

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Macrophages are immune cells responsible for tissue debridement and fighting infection. Clofazimine, an FDA-approved antibiotic, accumulates and precipitates as rod-shaped, crystal-like drug inclusions within macrophage lysosomes. Drug treatment as well as pathophysiological states could induce changes in macrophage mechanical property which in turn impact their phenotype and function. Here we report the use of acoustic tweezing cytometry as a new approach for in situ mechanical phenotyping of macrophages and for targeted macrophage cytotripsy. Acoustic tweezing cytometry applies ultrasound pulses to exert controlled forces to individual cells via integrin-bound microbubbles, enabling a creep test for measuring cellular mechanical property or inducing irreversible changes to the cells. Our results revealed that macrophages with crystal-like drug inclusions became significantly softer with higher cell compliance, and behaved more elastic with faster creep and recovery time constants. On the contrary, phagocytosis of solid polyethylene microbeads or treatment with soluble clofazimine rendered macrophages stiffer. Most notably, application of ultrasound pulses of longer duration and higher amplitude in ATC actuated the integrin-bound microbubbles to mobilize the crystal-like drug inclusions inside macrophages, turning the rod-shaped drug inclusions into intracellular microblender that effectively destructed the cells. This phenomenon of acoustic mechanopharmaceutical cytotripsy may be exploited for ultrasound activated, macrophage-directed drug release and delivery.

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Single-cell mechanics – An experimental–computational method for quantifying the membrane–cytoskeleton elasticity of cells

Cited by 14 publications

References 28 publications

EpCAM-Regulated Transcription Exerts Influences on Nanomechanical Properties of Endometrial Cancer Cells That Promote Epithelial-to-Mesenchymal Transition

EpCAM-Regulated Transcription Exerts Influences on Nanomechanical Properties of Endometrial Cancer Cells That Promote Epithelial-to-Mesenchymal Transition

The Mechanics of Single Cell and Collective Migration of Tumor Cells

Acoustic tweezing cytometry for mechanical phenotyping of macrophages and mechanopharmaceutical cytotripsy

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