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

Biophysical Journal
Michael MakRoger D Kamm

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.

Citations

Apr 6, 2018·Integrative Biology : Quantitative Biosciences From Nano to Macro·Jessica E KimMichael Mak
Nov 30, 2018·Soft Matter·Satish Kumar GuptaMing Guo
Sep 6, 2019·Interface Focus·Samantha G ZambutoBrendan A C Harley
Mar 11, 2021·Cell Reports·Benjamin YeomanAdam J Engler
Mar 26, 2021·Biomicrofluidics·P M GraybillR Mirzaeifar
Aug 7, 2021·Advanced Drug Delivery Reviews·Peiwen FuZhimin Tao
Sep 17, 2021·Cancer Research·Zeinab HajjarianSeemantini K Nadkarni
Oct 24, 2021·Biophysical Journal·Kathleen T DiNapoliPablo A Iglesias

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