Screening cell mechanotype by parallel microfiltration

Sci Rep. 2015 Dec 2:5:17595. doi: 10.1038/srep17595.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Epithelial-Mesenchymal Transition*
  • Female
  • Filtration / methods*
  • HL-60 Cells
  • Humans
  • Mice
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • Ovary* / metabolism
  • Ovary* / pathology
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics

Substances

  • Neoplasm Proteins
  • Transcription Factors