nn7b04567_si_004.mpg (1.38 MB)
Cancer Protrusions on a Tightrope: Nanofiber Curvature Contrast Quantitates Single Protrusion Dynamics
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posted on 2017-11-16, 00:00 authored by Brian Koons, Puja Sharma, Zhou Ye, Apratim Mukherjee, Meng Horng Lee, Denis Wirtz, Bahareh Behkam, Amrinder S. NainCell migration is
studied with the traditional focus on protrusion-driven
cell body displacement, while less is known on morphodynamics of individual
protrusions themselves, especially in fibrous environments mimicking
extracellular matrix. Here, using suspended fibers, we report integrative
and multiscale abilities to study protrusive behavior independent
of cell body migration. By manipulating the diameter of fibers in
orthogonal directions, we constrain cell migration along large diameter
(2 μm) base fibers, while solely allowing cells
to sense, initiate, and mature protrusions on orthogonally deposited
high-curvature/low diameter (∼100, 200, and 600 nm) protrusive fibers and low-curvature (∼300 and 600
nm width) protrusive flat ribbons. In doing so, we
report a set of morphodynamic metrics that precisely quantitate protrusion
dynamics. Protrusion growth and maturation occur by rapid broadening
at the base to achieve long lengths, a behavior dramatically influenced
by curvature. While flat ribbons universally induce the formation
of broad and long protrusions, we quantitatively protrutype protrusive behavior of two highly invasive cancer cell lines and
find breast adenocarcinoma (MDA-MB-231) to exhibit sensitivity to
fiber curvature higher than that of brain glioblastoma DBTRG-05MG.
Furthermore, while actin and microtubules localize within protrusions
of all sizes, we quantify protrusion size-driven localization of vimentin
and, contrary to current understanding, report that vimentin is not
required to form protrusions. Using multiple protrusive fibers, we
quantify high coordination between hierarchical branches of individual
protrusions and describe how the spatial configuration of multiple
protrusions regulates cell migratory state. Finally, we describe protrusion-driven
shedding and collection of cytoplasmic debris.
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protrutype protrusive behaviorprotrusive fibersprotrusion size-driven localizationMDA-MBstudy protrusive behaviorquantitate protrusion dynamicsbrain glioblastoma DBTRG -05MGcell body migrationcancer cell lines600 nm widthNanofiber Curvature Contrast Quantitates Single Protrusion Dynamics Cell migrationprotrusion-driven cell body displacement
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