Integrated Analysis of Intracellular Dynamics of MenaINV Cancer Cells in a 3D Matrix

Research output: Contribution to journalArticle

Authors

  • Michael Mak
  • Sarah Anderson
  • Meghan C. McDonough
  • Jessica E. Kim
  • Alexandra Boussommier-Calleja
  • Muhammad H. Zaman
  • Roger D. Kamm

Colleges, School and Institutes

External organisations

  • Harvey Mudd College
  • Department of Biomedical Engineering, Yale University
  • Department of Mechanical Engineering, Massachusetts Institute of Technology
  • Department of Biomedical Engineering, Boston University, Boston MA 02215.
  • Howard Hughes Medical Institute, Boston University

Abstract

The intracellular environment is composed of a filamentous network that exhibits dynamic turnover of cytoskeletal components and internal force generation from molecular motors. Particle tracking microrheology enables a means to probe the internal mechanics and dynamics. Here, we develop an analytical model to capture the basic features of the active intracellular mechanical environment, including both thermal and motor-driven effects, and show consistency with a diverse range of experimental microrheology data. We further perform microrheology experiments, integrated with Brownian dynamics simulations of the active cytoskeleton, on metastatic breast cancer cells embedded in a three-dimensional collagen matrix with and without the presence of epidermal growth factor to probe the intracellular mechanical response in a physiologically mimicking scenario. Our results demonstrate that EGF stimulation can alter intracellular stiffness and power output from molecular motor-driven fluctuations in cells overexpressing an invasive isoform of the actin-associated protein Mena.

Details

Original languageEnglish
Pages (from-to)1874-1884
Number of pages11
JournalBiophysical Journal
Volume112
Issue number9
Publication statusPublished - 9 May 2017

ASJC Scopus subject areas