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

Autor:	Mak M; Department of Biomedical Engineering, Yale University, New Haven, Connecticut; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; Department of Biomedical Engineering, Boston University, Boston, Massachusetts. Electronic address: michael.mak@yale.edu., Anderson S; Harvey Mudd College, Claremont, California., McDonough MC; Department of Biomedical Engineering, Boston University, Boston, Massachusetts., Spill F; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; Department of Biomedical Engineering, Boston University, Boston, Massachusetts., Kim JE; Department of Biomedical Engineering, Boston University, Boston, Massachusetts., Boussommier-Calleja A; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts., Zaman MH; Department of Biomedical Engineering, Boston University, Boston, Massachusetts; Howard Hughes Medical Institute, Boston University, Boston, Massachusetts. Electronic address: zaman@bu.edu., Kamm RD; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts. Electronic address: rdkamm@mit.edu.
Jazyk:	angličtina
Zdroj:	Biophysical journal [Biophys J] 2017 May 09; Vol. 112 (9), pp. 1874-1884.
DOI:	10.1016/j.bpj.2017.03.030
Abstrakt:	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. (Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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