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Atomic force microscopy-based microrheology reveals significant differences in the viscoelastic response between malign and benign cell lines.

Rother J, Nöding H, Mey I, Janshoff A - Open Biol (2014)

Bottom Line: Mechanical phenotyping of cells by atomic force microscopy (AFM) was proposed as a novel tool in cancer cell research as cancer cells undergo massive structural changes, comprising remodelling of the cytoskeleton and changes of their adhesive properties.In this work, we focused on the mechanical properties of human breast cell lines with different metastatic potential by AFM-based microrheology experiments.Including also other cell lines from different organs shows that the loss tangent (G″/G') increases generally with the metastatic potential from MCF-10A representing benign cells to highly malignant MDA-MB-231 cells.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physical Chemistry, Tammannstrasse 6, 37077 Göttingen, Germany.

ABSTRACT
Mechanical phenotyping of cells by atomic force microscopy (AFM) was proposed as a novel tool in cancer cell research as cancer cells undergo massive structural changes, comprising remodelling of the cytoskeleton and changes of their adhesive properties. In this work, we focused on the mechanical properties of human breast cell lines with different metastatic potential by AFM-based microrheology experiments. Using this technique, we are not only able to quantify the mechanical properties of living cells in the context of malignancy, but we also obtain a descriptor, namely the loss tangent, which provides model-independent information about the metastatic potential of the cell line. Including also other cell lines from different organs shows that the loss tangent (G″/G') increases generally with the metastatic potential from MCF-10A representing benign cells to highly malignant MDA-MB-231 cells.

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Related in: MedlinePlus

(a) AFM-deflection images of MCF-10A, MCF-7 and MDA-MB-231. Cells were imaged in constant force mode using pyramidal cantilever-tip geometry. (b) Median values of the storage modulus G′ (filled symbols) and loss modulus G″ (open symbols) as a function of oscillation frequency (two force maps, more than 10 cells). The data of the complex shear modulus were fitted using the power-law structural damping model (solid lines).
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RSOB140046F3: (a) AFM-deflection images of MCF-10A, MCF-7 and MDA-MB-231. Cells were imaged in constant force mode using pyramidal cantilever-tip geometry. (b) Median values of the storage modulus G′ (filled symbols) and loss modulus G″ (open symbols) as a function of oscillation frequency (two force maps, more than 10 cells). The data of the complex shear modulus were fitted using the power-law structural damping model (solid lines).

Mentions: To investigate the frequency-dependent mechanical response of cancer cells compared with normal cells, we chose eight cell lines from four different organs. MDCKII cells and CaKi-1 cells originate from the kidney; SW13 are derived from the adrenal gland; NMuMG, MCF-10A, MCF-7 and MDA-MB-231 are cells from the mammary gland, and A549 cells are derived from the lung epithelial layer. MDCKII and NMuMG cells show epithelial morphology, growing as a confluent monolayer with strong intercellular junctions and a pronounced apical–basal polarity [21]. MCF-10 is an immortal non-tumorigenic epithelial cell line derived from benign breast tissue. Although the cells are immortal, they display a normal, non-cancerous phenotype. MCF-7 cells grow in a dense monolayer but also showed the ability to form metastasis in lung, liver and spleen in athymic nude mice [22]. Although forming a confluent, polarized monolayer is a characteristic of normal epithelial cells, the CaKi-1 is a representative metastatic renal cancer cell line [23]. Similarly, MDA-MB-231 cells are considered to be malignant cancer cells derived from the mammary gland, forming metastases in various organs, including lung and bones [24]. The A549 cell line originates from non-small-cell lung cancer adenocarcinoma cells and shows an epithelial-like morphology. However, in contrast to the two epithelial cell lines used in this study, the A549 cells bear the potential to form metastasis in in vivo models [25]. SW13 cells belong to the small-cell carcinoma and are derived from the adrenal gland [26]. Apart from the aforementioned cell lines, we also investigated fibroblasts as a paradigm for a benign mesenchymal cell as well as MCF-10A cells representing non-tumorigenic cells. Representative AFM-deflection images of all cell lines can be found in figure 3a (MCF-10A, MCF-7, MDA-MB-231) and in the electronic supplementary material, figure S3.Figure 3.


Atomic force microscopy-based microrheology reveals significant differences in the viscoelastic response between malign and benign cell lines.

Rother J, Nöding H, Mey I, Janshoff A - Open Biol (2014)

(a) AFM-deflection images of MCF-10A, MCF-7 and MDA-MB-231. Cells were imaged in constant force mode using pyramidal cantilever-tip geometry. (b) Median values of the storage modulus G′ (filled symbols) and loss modulus G″ (open symbols) as a function of oscillation frequency (two force maps, more than 10 cells). The data of the complex shear modulus were fitted using the power-law structural damping model (solid lines).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042852&req=5

RSOB140046F3: (a) AFM-deflection images of MCF-10A, MCF-7 and MDA-MB-231. Cells were imaged in constant force mode using pyramidal cantilever-tip geometry. (b) Median values of the storage modulus G′ (filled symbols) and loss modulus G″ (open symbols) as a function of oscillation frequency (two force maps, more than 10 cells). The data of the complex shear modulus were fitted using the power-law structural damping model (solid lines).
Mentions: To investigate the frequency-dependent mechanical response of cancer cells compared with normal cells, we chose eight cell lines from four different organs. MDCKII cells and CaKi-1 cells originate from the kidney; SW13 are derived from the adrenal gland; NMuMG, MCF-10A, MCF-7 and MDA-MB-231 are cells from the mammary gland, and A549 cells are derived from the lung epithelial layer. MDCKII and NMuMG cells show epithelial morphology, growing as a confluent monolayer with strong intercellular junctions and a pronounced apical–basal polarity [21]. MCF-10 is an immortal non-tumorigenic epithelial cell line derived from benign breast tissue. Although the cells are immortal, they display a normal, non-cancerous phenotype. MCF-7 cells grow in a dense monolayer but also showed the ability to form metastasis in lung, liver and spleen in athymic nude mice [22]. Although forming a confluent, polarized monolayer is a characteristic of normal epithelial cells, the CaKi-1 is a representative metastatic renal cancer cell line [23]. Similarly, MDA-MB-231 cells are considered to be malignant cancer cells derived from the mammary gland, forming metastases in various organs, including lung and bones [24]. The A549 cell line originates from non-small-cell lung cancer adenocarcinoma cells and shows an epithelial-like morphology. However, in contrast to the two epithelial cell lines used in this study, the A549 cells bear the potential to form metastasis in in vivo models [25]. SW13 cells belong to the small-cell carcinoma and are derived from the adrenal gland [26]. Apart from the aforementioned cell lines, we also investigated fibroblasts as a paradigm for a benign mesenchymal cell as well as MCF-10A cells representing non-tumorigenic cells. Representative AFM-deflection images of all cell lines can be found in figure 3a (MCF-10A, MCF-7, MDA-MB-231) and in the electronic supplementary material, figure S3.Figure 3.

Bottom Line: Mechanical phenotyping of cells by atomic force microscopy (AFM) was proposed as a novel tool in cancer cell research as cancer cells undergo massive structural changes, comprising remodelling of the cytoskeleton and changes of their adhesive properties.In this work, we focused on the mechanical properties of human breast cell lines with different metastatic potential by AFM-based microrheology experiments.Including also other cell lines from different organs shows that the loss tangent (G″/G') increases generally with the metastatic potential from MCF-10A representing benign cells to highly malignant MDA-MB-231 cells.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physical Chemistry, Tammannstrasse 6, 37077 Göttingen, Germany.

ABSTRACT
Mechanical phenotyping of cells by atomic force microscopy (AFM) was proposed as a novel tool in cancer cell research as cancer cells undergo massive structural changes, comprising remodelling of the cytoskeleton and changes of their adhesive properties. In this work, we focused on the mechanical properties of human breast cell lines with different metastatic potential by AFM-based microrheology experiments. Using this technique, we are not only able to quantify the mechanical properties of living cells in the context of malignancy, but we also obtain a descriptor, namely the loss tangent, which provides model-independent information about the metastatic potential of the cell line. Including also other cell lines from different organs shows that the loss tangent (G″/G') increases generally with the metastatic potential from MCF-10A representing benign cells to highly malignant MDA-MB-231 cells.

Show MeSH
Related in: MedlinePlus