title: A high throughput approach for analysis of cell nuclear deformability at single cell level.
abstract: 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.
authors.affiliation: BIOMATEN, METU Centre of Excellence in Biomaterials and Tissue Engineering, 06800, Ankara, Turkey.|METU Department of Biomedical Engineering, 06800, Ankara, Turkey.
authors.forename: Menekse
authors.initials: M
authors.lastname: Ermis
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Derya
authors.initials: D
authors.lastname: Akkaynak
authors.affiliation: 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.
authors.forename: Pu
authors.initials: P
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Utkan
authors.initials: U
authors.lastname: Demirci
authors.affiliation: BIOMATEN, METU Centre of Excellence in Biomaterials and Tissue Engineering, 06800, Ankara, Turkey.|METU Department of Biomedical Engineering, 06800, Ankara, Turkey.|METU Department of Biological Sciences, 06800, Ankara, Turkey.
authors.forename: Vasif
authors.initials: V
authors.lastname: Hasirci
mesh_terms: D000465:Algorithms; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000502:physiology*; D004548:Elasticity; D006801:Humans; D061986:MCF-7 Cells; D059010:Single-Cell Analysis / Q000295:instrumentation* / Q000379:methods; D013314:Stress, Mechanical