title: Screening cell mechanotype by parallel microfiltration.
abstract: Cell mechanical phenotype or 'mechanotype' is emerging as a valuable label-free biomarker. For example, marked changes in the viscoelastic characteristics of cells occur during malignant transformation and cancer progression. Here we describe a simple and scalable technique to measure cell mechanotype: this parallel microfiltration assay enables multiple samples to be simultaneously measured by driving cell suspensions through porous membranes. To validate the method, we compare the filtration of untransformed and HRas(V12)-transformed murine ovary cells and find significantly increased deformability of the transformed cells. Inducing epithelial-to-mesenchymal transition (EMT) in human ovarian cancer cells by overexpression of key transcription factors (Snail, Slug, Zeb1) or by acquiring drug resistance produces a similar increase in deformability. Mechanistically, we show that EMT-mediated changes in epithelial (loss of E-Cadherin) and mesenchymal markers (vimentin induction) correlate with altered mechanotype. Our results demonstrate a method to screen cell mechanotype that has potential for broader clinical application.
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, USA.
authors.forename: Dongping
authors.initials: D
authors.lastname: Qi
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, USA.
authors.forename: Navjot
authors.initials: N
authors.lastname: Kaur Gill
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
authors.forename: Chintda
authors.initials: C
authors.lastname: Santiskulvong
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Sifuentes
authors.affiliation: Department of Obstetrics and Gynecology, Division Gynecologic Oncology, Stanford Cancer Institute, Stanford University, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Dorigo
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
authors.affiliation: Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, USA.
authors.forename: Barbie
authors.initials: B
authors.lastname: Taylor-Harding
authors.affiliation: Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, USA.|Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, USA.
authors.forename: W
authors.initials: W
authors.lastname: Ruprecht Wiedemeyer
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Rowat
mesh_terms: D000818:Animals; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005374:Filtration / Q000379:methods*; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; D014157:Transcription Factors