AFM nano-mechanics and calcium dynamics of prostate cancer cells with distinct metastatic potential

Bastatas, Lyndon D.; Martinez-Marin, Dalia; Matthews, James R.; Hashem, Jood; Lee, Yong J.; Sennoune, Souad R.; Filleur, Stéphanie; Martı́nez-Zaguilán, Raul; Park, Soyeun

doi:10.1016/j.bbagen.2012.02.006

Cited by 84 publications

(85 citation statements)

References 57 publications

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“…There is probably no disease that does not involve a change in the shape of some cells, and that can only occur through changes in force. These induced changes can have direct effects, as in athletic injuries, traumatic brain injury, or muscular dystrophy, or indirectly, as in the mechanical changes noted for metastatic cancer cells (39) or in anemia (40,41).…”

Section: Discussionmentioning

confidence: 99%

Actin stress in cell reprogramming

Guo

Wang

Sachs

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

103

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Cell mechanics plays a role in stem cell reprogramming and differentiation. To understand this process better, we created a genetically encoded optical probe, named actin-cpstFRET-actin (AcpA), to report forces in actin in living cells in real time. We showed that stemness was associated with increased force in actin. We reprogrammed HEK-293 cells into stem-like cells using no transcription factors but simply by softening the substrate. However, Madin-Darby canine kidney (MDCK) cell reprogramming required, in addition to a soft substrate, Harvey rat sarcoma viral oncogene homolog expression. Replating the stem-like cells on glass led to redifferentiation and reduced force in actin. The actin force probe was a FRET sensor, called cpstFRET (circularly permuted stretch sensitive FRET), flanked by g-actin subunits. The labeled actin expressed efficiently in HEK, MDCK, 3T3, and bovine aortic endothelial cells and in multiple stable cell lines created from those cells. The viability of the cell lines demonstrated that labeled actin did not significantly affect cell physiology. The labeled actin distribution was similar to that observed with GFPtagged actin. We also examined the stress in the actin cross-linker actinin. Actinin force was not always correlated with actin force, emphasizing the need for addressing protein specificity when discussing forces. Because actin is a primary structural protein in animal cells, understanding its force distribution is central to understanding animal cell physiology and the many linked reactions such as stress-induced gene expression. This new probe permits measuring actin forces in a wide range of experiments on preparations ranging from isolated proteins to transgenic animals.actin | force probe | stem cell | reprogramming | cell mechanics C ells have only three sources of free energy-chemical, electrical, and mechanical potential (1)-and life is driven by the flow of energy between them. The flow of mechanical energy has not been well studied in living cells outside of muscle, yet all cells are subject to endogenous and exogenous mechanical forces. The lack of progress in measuring these forces (stress) has primarily been due to a lack of suitable probes, but that has now been remedied with the development of genetically coded FRETbased force sensors (2). The literature shows many macroscopic effects of mechanical stress on cellular processes including cell motility, embryogenesis, stem cell replication and differentiation (3, 4), bone and muscle homeostasis, gene expression, protein folding (5), and membrane potential (6). However, these studies lacked the ability to measure stress in specific structural proteins, and the analyses have tended to treat cytoskeletal stresses as uniform, which we now know is not true (2, 7). We, and other groups (8), have shown that the distribution of forces is nonuniform in both time and space and protein specificity (9).The force sensors consist of a FRET pair (typically CFP/ YFP) connected by a protein linker, a biological analog of a mechanic...

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Section: Discussionmentioning

confidence: 99%

Actin stress in cell reprogramming

Guo

Wang

Sachs

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

103

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“…However, the opposite correlation-the reinforced mechanical stiffness for motile phenotypes-was observed from prostate and ovarian cancer cells. [30][31][32]43) The elastic moduli of these cancer cells lie in the lower spectrum (< 500 Pa) compared to others and thus the further decrease in the elastic moduli may not be optimal for the effective invasion. This two different correlations could be associated with differences in mechanisms governing the cellular motility-a bleb-associated migration through actomyosin contractility vs. an elongated migration through actin polymerization.…”

Section: Discussionmentioning

confidence: 99%

“…[26][27][28][29] On the contrary, the opposite correlation has been reported specially for prostate cancer cells. [30][31][32] Since the mechanical stiffness was suggested as a diagnostic marker for oral cancer cells, 33) several studies examined its possible use for prognosis. 34,35) A recent study using AFM reported the reduction of mechanical stiffness in metastatic tongue squamous cells due to changes in actin filaments and microtubules.…”

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confidence: 99%

Nano-biomechanical Validation of Epithelial–Mesenchymal Transition in Oral Squamous Cell Carcinomas

Park

Jang

Jeong

2016

Biological & Pharmaceutical Bulletin

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The effective cure for oral squamous cell carcinoma (OSCC) patients is challenging due late diagnosis and fatal metastasis. The standard diagnosis for OSCC often depends on the subjective interpretation of conventional histopathology. Additionally, there is no standard way for OSCC prognosis. Over the past decade, nano-mechanical stiffness has been considered as a quantitative measure for cancer diagnosis. Nevertheless, its application to OSCC diagnosis and prognosis is still in a primitive stage. In this study, we investigated whether the OSCC progression can be predicted by nano-mechanical properties in combination with biochemical properties, especially the epithelial-mesenchymal transition (EMT). Atomic force microscopy-based nano-mechanical measurements of three different OSCC cell lines-SCC-4, SCC-9, and SCC-15-were conducted together with biochemical analyses. The gradual upregulation of Snail2, N-cadherin, and vimentin and the simultaneous downregulation of E-cadherin were observed, and the degree of upregulation and downregulation was stronger in the order of the cell lines mentioned above. The strength of enhancement in migration was in the same order as well. Consistently, nano-mechanical stiffness was gradually decreased as the EMT progresses. These results suggest that the nano-mechanical assay could serve as a quantitative tool to predict the OSCC progression in the context of the EMT. Furthermore, we found that the upregulated vimentin, a major filamentous component of the cytoskeleton, may contribute to mechanical softening, which can be discerned from the role of actin filaments in mechanical stiffness. In conclusion, our combinational study proposes a novel way to elucidate the mechanism of OSCC progression and its therapeutic targets.Key words nano-mechanics; epithelial-mesenchymal transition; atomic force microscopy; oral cancer Oral squamous cell carcinoma (OSCC) is the most common neoplasm of the head and neck squamous cell carcinoma (HNSCC), which represents approximately 6% of all types of cancer. Also about half a million new cases are diagnosed every year.1) It is a highly invasive malignant tumor characterized by a high rate of metastasis to the cervical lymph nodes.2) Diagnosis and management of OSCC have improved by combining therapies such as radical surgery, radiotherapy and neo-adjuvant chemotherapy, but the overall 5-year survival rate is still below 50% because of late diagnosis and high rate of recurrence.3,4) Thus, it is highly desirable to understand the underlying mechanism governing metastatic dissemination of OSCC for the development of anticancer therapeutics.The progression of OSCC is largely dependent on the epithelial-mesenchymal transition (EMT). 5,6) Recent studies have reported that the EMT has been strongly associated with cancer cell stemness 7,8) and chemoresistance to anti-cancer drugs, [9][10][11][12] indicating that targeting EMT could be a good strategy to overcome cancer metastasis. Notably, transforming growth factor-β1 (TGF-β1) has been known to be a prima...

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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. The results showed that Young's modulus alone failed to indicate the metastatic progression, but the combined biomechanical signatures of Young's modulus, adhesion, and calcium dynamics could effectively indicate the metastatic potential of prostate cancer cells, inspiring that performing studies on measuring multiple types of cell mechanics (e.g., Young's modulus, adhesion, relaxation time) and combining them with biological properties may help us to develop better biomarkers (or biomarker combination) for exactly indicating cell states and pathological changes.…”

Section: Discussion and Perspectivementioning

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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AFM nano-mechanics and calcium dynamics of prostate cancer cells with distinct metastatic potential

Cited by 84 publications

References 57 publications

Actin stress in cell reprogramming

Actin stress in cell reprogramming

Nano-biomechanical Validation of Epithelial–Mesenchymal Transition in Oral Squamous Cell Carcinomas

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

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