Open AccessDirected invasion of cancer cell spheroids inside 3D collagen matrices oriented by microfluidic flow in experiment and simulation
Author(s) -
Florian Geiger,
Lukas G. Schnitzler,
Manuel Brugger,
Christoph Westerhausen,
Hanna Engelke
Publication year - 2022
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0264571
Subject(s) - spheroid , microfluidics , extracellular matrix , fiber , biophysics , materials science , orientation (vector space) , matrix (chemical analysis) , perpendicular , brownian motion , chemistry , nanotechnology , biology , physics , composite material , geometry , in vitro , biochemistry , quantum mechanics , mathematics
Invasion is strongly influenced by the mechanical properties of the extracellular matrix. Here, we use microfluidics to align fibers of a collagen matrix and study the influence of fiber orientation on invasion from a cancer cell spheroid. The microfluidic setup allows for highly oriented collagen fibers of tangential and radial orientation with respect to the spheroid, which can be described by finite element simulations. In invasion experiments, we observe a strong bias of invasion towards radial as compared to tangential fiber orientation. Simulations of the invasive behavior with a Brownian diffusion model suggest complete blockage of migration perpendicularly to fibers allowing for migration exclusively along fibers. This slows invasion toward areas with tangentially oriented fibers down, but does not prevent it.