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

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

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

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

ASJC Scopus subject areas

  • Biophysics

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