An investigation of the viscoelastic properties and the actin cytoskeletal structure of triple negative breast cancer cells

Hu, Jingjie; Zhou, Yuxiao; Obayemi, John D.; Du, Jinglei; Soboyejo, Winston O.

doi:10.1016/j.jmbbm.2018.05.038

Cited by 32 publications

(51 citation statements)

References 90 publications

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“…Cytoskeletal changes in chondrocytes, osteoblasts, adipocytes, as well as breast cancer cells directly affect cellular viscoelasticity. [45][46][47] As in our study, earlier studies have found that the viscoelastic deformation of cells increases with the applied loading amplitude and cyclic loading duration. 48,49 The lipid bilayer of the plasma membrane is also known to have viscoelasticity properties, 50 which influence lipid-protein or protein-protein interaction-induced cell signaling at the membrane surface.…”

Section: Discussionsupporting

confidence: 80%

High shear stress amplitude in combination with prolonged stimulus duration determine induction of osteoclast formation by hematopoietic progenitor cells

et al. 2020

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To date, it is unclear how fluid dynamics stimulate mechanosensory cells to induce an osteoprotective or osteodestructive response. We investigated how murine hematopoietic progenitor cells respond to 2 minutes of dynamic fluid flow stimulation with a precisely controlled sequence of fluid shear stresses. The response was quantified by measuring extracellular adenosine triphosphate (ATP), immunocytochemistry of Piezo1, and sarcoplasmic/endoplasmic Ca2+ reticulum ATPase 2 (SERCA2), and by the ability of soluble factors produced by mechanically stimulated cells to modulate osteoclast differentiation. We rejected our initial hypothesis that peak wall shear stress rate determines the response of hematopoietic progenitor cells to dynamic fluid shear stress, as it had only a minor correlation with the abovementioned parameters. Low stimulus amplitudes corresponded to activation of Piezo1, SERCA2, low concentrations of extracellular ATP, and inhibition of osteoclastogenesis and resorption area, while high amplitudes generally corresponded to osteodestructive responses. At a given amplitude (3 Pa) and waveform (square), the duration of individual stimuli (duty cycle) showed a strong correlation with the release of ATP and osteoclast number and resorption area. Collectively, our data suggest that hematopoietic progenitor cells respond in a viscoelastic manner to loading, since a combination of high shear stress amplitude and prolonged duty cycle is needed to trigger an osteodestructive response. Plain Language Summary In case of painful joints or missing teeth, the current intervention is to replace them with an implant to keep a high‐quality lifestyle. When exercising or chewing, the cells in the bone around the implant experience mechanical loading. This loading generally supports bone formation to strengthen the bone and prevent breaking, but can also stimulate bone loss when the mechanical loading becomes too high around orthopedic and dental implants. We still do not fully understand how cells in the bone can distinguish between mechanical loading that strengthens or weakens the bone. We cultured cells derived from the bone marrow in the laboratory to test whether the bone loss response depends on (i) how fast a mechanical load is applied (rate), (ii) how intense the mechanical load is (amplitude), or (iii) how long each individual loading stimulus is applied (duration). We mimicked mechanical loading as it occurs in the body, by applying very precisely controlled flow of fluid over the cells. We found that a mechanosensitive receptor Piezo1 was activated by a low amplitude stimulus, which usually strengthens the bone. The potential inhibitor of Piezo1, namely SERCA2, was only activated by a low amplitude stimulus. This happened regardless of the rate of application. At a constant high amplitude, a longer duration of the stimulus enhanced the bone‐weakening response. Based on these results we deduce that a high loading amplitude tends to be bone weakening, and the longer this high amplitude persists, the wor...

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Section: Discussionsupporting

confidence: 80%

High shear stress amplitude in combination with prolonged stimulus duration determine induction of osteoclast formation by hematopoietic progenitor cells

et al. 2020

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“…3,10 Regarding the obtained results, cell stiffening by substrate rigidity was accompanied by more stress fibers and increased migration ability. 3,10 Regarding the obtained results, cell stiffening by substrate rigidity was accompanied by more stress fibers and increased migration ability.…”

Section: Discussionmentioning

confidence: 71%

“…Investigating the relation between cell biomechanics and human abnormalities has garnered much interest in recent years. 3,7 Young's modulus of highly invasive breast cancer cells was reported significantly lower than noninvasive breast cancer cells. Previous studies show that cancer cells express different mechanical and physical properties compared to healthy cells.…”

Section: Introductionmentioning

confidence: 99%

“…5,6 There are several studies that have demonstrated softening of cancerous cells such that mechanical properties of cancer cells correlate to their invasiveness. 3,7 Young's modulus of highly invasive breast cancer cells was reported significantly lower than noninvasive breast cancer cells. 8 These findings suggest that cellular mechanics strongly correlates with the cancer invasiveness, and Young's modulus might be an indicator of cancer cell invasiveness.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies show that cancer cells express different mechanical and physical properties compared to healthy cells. 3,4 The smaller Young's modulus and increased cell deformability are major characteristics of cancer cells. 5,6 There are several studies that have demonstrated softening of cancerous cells such that mechanical properties of cancer cells correlate to their invasiveness.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations

Azadi

Tafazzoli-Shadpour

Soleimani

et al. 2019

J Biomedical Materials Res

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To date, a myriad of strategies has been suggested for targeting the chemical signaling of cancer cells. Also, biomechanical features are gaining much more attention. These features can be used as biomarkers which influence cancer progression. Current approaches on cancer treatment are mainly focused on changing the biochemical signaling of cancer cells, whereas less attention was devoted to their biomechanical properties. Herein, we propose targeting of cancer cell mechanics through the microenvironmental mechanical and chemical cues. As such, we examined the role of substrate stiffness as well as the effect of epidermal growth factor receptor (EGFR) blockade in the cell mechanics. As a mechanical stimulus, stiff and soft polydimethylsiloxane substrates were utilized, while as a chemical stimulus, EGFR blockade was considered. Thus, breast cancer cell lines, MCF7 and MDA‐MB‐231, were cultured among chemical and mechanical groups. The local elasticity of cancer cells was assessed by atomic force microscopy nanoindentation method. Furthermore, we evaluated the effect of mentioned mechanical and chemical treatments on the morphology, actin cytoskeleton structures, and cancer cell migration abilities. The stiffness and migration ability of cancer cells increased by substrate stiffening while Cetuximab treatment demonstrated an elevation in the elastic modulus of cells followed by a reduction in the migration ability. These findings indicate that cancer cell mechanics is modulated not only by the mechanical cues but also by the chemical ones through EGFR signaling pathway. Overall, our results illustrate that manipulation of cell mechanics allows for the possible modulation of tumor cell migration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1569–1581, 2019.

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Investigation of creep properties and the cytoskeletal structures of non‐tumorigenic breast cells and triple‐negative breast cancer cells

Onwudiwe

Obayemi

et al. 2021

J Biomedical Materials Res

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This article presents the correlation of creep and viscoelastic properties to the cytoskeletal structure of both tumorigenic and non‐tumorigenic cells. Unique shear assay and strain mapping techniques were used to study the creep and viscoelastic properties of single non‐tumorigenic and tumorigenic cells. At least 20 individual cells, three locations per cell, were studied. From the results, lower densities in the volume of actin, and keratin 18 structures were observed with the progression of cancer and were correlated to the increased creep rates and reduced mechanical properties (Young's moduli and viscosities) of tumorigenic (MDA‐MB‐231) cells. The study reveals significant differences between the creep and viscoelastic properties of non‐tumorigenic breast cells versus tumorigenic cells. The variations in the creep strain rates are shown to be well characterized by lognormal distributions, while the statistical variations in the viscoelastic properties are well‐described by normal distributions. The implications of the results are discussed for the study of discrete cell behaviors, strain and viscoelastic responses of the cell, and the role of cell cytoskeleton in the onset and progression of cancers.

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An investigation of the viscoelastic properties and the actin cytoskeletal structure of triple negative breast cancer cells

Cited by 32 publications

References 90 publications

High shear stress amplitude in combination with prolonged stimulus duration determine induction of osteoclast formation by hematopoietic progenitor cells

High shear stress amplitude in combination with prolonged stimulus duration determine induction of osteoclast formation by hematopoietic progenitor cells

Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations

Investigation of creep properties and the cytoskeletal structures of non‐tumorigenic breast cells and triple‐negative breast cancer cells

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