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

Biophys J. 2017 May 9;112(9):1874-1884. doi: 10.1016/j.bpj.2017.03.030.

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.

MeSH terms

  • Adenocarcinoma / metabolism
  • Algorithms
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Collagen
  • Computer Simulation
  • Cytoskeleton / metabolism
  • Epidermal Growth Factor / administration & dosage
  • Epidermal Growth Factor / metabolism
  • Humans
  • Intracellular Space / metabolism*
  • Microfilament Proteins / metabolism
  • Mitochondria / metabolism
  • Models, Biological
  • Motion
  • Rheology
  • Tissue Scaffolds

Substances

  • Enah protein, human
  • Microfilament Proteins
  • Epidermal Growth Factor
  • Collagen