Amplification of nuclear deformation of breast cancer cells by seeding on micropattemed surfaces to better distinguish their malignancies

2019-11-01
Antmen Altunsoy, Ezgi
Demirci, Utkan
Hasırcı, Vasıf Nejat
Information about the mechanical properties of cancer cells leads to new insights about their malignancy levels. The more flexible the cancer cells and their nuclei are, the more aggressive and invasive they are. Flexibility is a result of composition and properties of molecular constituents of cells and its extent is expressed by deformation. Differences in the mechanical properties could be modulated by topography and chemistry of the substrate. In this study, the main hypothesis is that the difference in the mechanical properties of malignant and benign breast cancer cells could be used as a discriminator of these cells and reflected by the extent of nuclear deformation on micropattemed substrates. We compared benign (MCF10A), malignantnoninvasive (MCF7), and malignant highly invasive (MDAMB231) breast cancer cell lines using their nuclear deformability on micropattemed surfaces designed with square prism-shaped micropillars of poly(methyl methacrylate) (PMMA) (8 mu m high, 4 x 4 mu m(2) area, 4 mu m gap). Several shape descriptors (circularity, solidity, roundness, aspect ratio) were used to analyze nuclear deformation. We were able to discriminate the three cells when the descriptor circularity and hydrophobic micropattemed surfaces were used. The cells showed nuclear deformability in the order following the extent of their malignancies. The most aggressive cell, MDAMB231, had the lowest circularity value, 0.37, whereas the noninvasive malignant, MCF7, and benign, MCF10A, cells had higher values 0.47 and 0.77, respectively. Mechanism of the deformation was shown at the molecular level that the expression of Lamin A/C and Nesprin-2 genes decreased with increased nuclear deformation. In summary, biomechanical properties of cells can provide useful information about their cancer state and they can be reflected in the biological markers.
COLLOIDS AND SURFACES B-BIOINTERFACES

Suggestions

Enrichment of MCF7 breast cancer cells from leukocytes through continuous flow dielectrophoresis
Çağlayan, Zeynep; Külah, Haluk; Department of Electrical and Electronics Engineering (2018)
Circulating tumor cells (CTCs) are cancerous cells detached from a primary tumor site and enter the bloodstream, causing the development of new tumors in a secondary site. Therefore, their detection in blood is critical to assess the metastatic progression and to guide the line of the therapy. However, the rarity of CTCs in the bloodstream and the lack of suitable detection tool hinders their use as a biomarker in malignancies. Recent advances in microfluidic technologies enabled development of point-of-car...
Targeted delivery of CPG-oligodeoxynucleotide to breast cancer cells by poly-amidoamine dendrimer-modified magnetic nanoparticles
Taghavi Pourianazar, Negar; Gündüz, Ufuk; Gündüz, Güngör; Department of Biotechnology (2016)
One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which...
Identification of gene mutations involved in drug resistance in liver cancer using RNA-SEQ data analysis
Shojaei, Mona; Atalay, Rengül; Acar, Aybar Can; Department of Bioinformatics (2016)
A significant concern in cancer research is the detection of cancer associated somatic mutations. Liver cancer is the 5th most common and 2nd deadliest cancer in the world. Several somatic mutations were previously reported in liver cancer but their relations to chemotherapeutic response was not studied in detail. In this study, the relationship between mutation status and drug treatment response of well-differentiated Huh7 and poorly-differentiated Mahlavu liver cancer cells were analyzed. The RNA-Seq data...
Investigation of the molecular pathways involved in intestinal epithelial differentiation
Sade Memişoğlu, Aslı; Banerjee, Sreeparna; Department of Biology (2014)
The molecular mechanisms of balanced and continuous generation of intestinal epithelial cells, is poorly understood and disruption of this balance may result in neoplastic transformation and malignant growth. Differentiation is regulated by numerous signals, which in turn regulate signaling pathways directing activation or inactivation of certain transcription factors. Perturbations like changes in Ca2+ levels, glucose or amino acid starvation result in an ER stress response, which is also implicated in the...
A high throughput approach for analysis of cell nuclear deformability at single cell level
Ermis, Menekse; Akkaynak, Derya; Chen, Pu; Demirci, Utkan; Hasırcı, Vasıf Nejat (2016-11-14)
Various physiological and pathological processes, such as cell differentiation, migration, attachment, and metastasis are highly dependent on nuclear elasticity. Nuclear morphology directly reflects the elasticity of the nucleus. We propose that quantification of changes in nuclear morphology on surfaces with defined topography will enable us to assess nuclear elasticity and deformability. Here, we used soft lithography techniques to produce 3 dimensional (3-D) cell culture substrates decorated with micron ...
Citation Formats
E. Antmen Altunsoy, U. Demirci, and V. N. Hasırcı, “Amplification of nuclear deformation of breast cancer cells by seeding on micropattemed surfaces to better distinguish their malignancies,” COLLOIDS AND SURFACES B-BIOINTERFACES, pp. 0–0, 2019, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/31197.