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Sci Rep. 2016 Nov 14;6:36917. doi: 10.1038/srep36917.

A high throughput approach for analysis of cell nuclear deformability at single cell level.

Author information

BIOMATEN, METU Centre of Excellence in Biomaterials and Tissue Engineering, 06800, Ankara, Turkey.
METU Department of Biomedical Engineering, 06800, Ankara, Turkey.
Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Canary Center at Stanford for Early Cancer Detection, Department of Radiology, School of Medicine, Stanford University, Palo Alto, CA, 94304, USA.
Department of Electrical Engineering (by courtesy), Stanford University, Stanford, CA, USA.
METU Department of Biological Sciences, 06800, Ankara, Turkey.


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 sized pillar structures of variable aspect ratios and dimensions to induce changes in cellular and nuclear morphology. We developed a high content image analysis algorithm to quantify changes in nuclear morphology at the single-cell level in response to physical cues from the 3-D culture substrate. We present that nuclear stiffness can be used as a physical parameter to evaluate cancer cells based on their lineage and in comparison to non-cancerous cells originating from the same tissue type. This methodology can be exploited for systematic study of mechanical characteristics of large cell populations complementing conventional tools such as atomic force microscopy and nanoindentation.

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Conflict of interest statement

The authors M.E., D.A., P.C. and V.H. declare no competing financial interests. U.D. is a founder of, and has an equity interest in: (i) DxNow Inc., a company that is developing microfluidic and imaging technologies for point-of-care diagnostic solutions, and (ii) Koek Biotech, a company that is developing microfl uidic IVF technologies for clinical solutions. U.D.’s interests were viewed and managed in accordance with the conflict of interest policies.

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