3 research outputs found
Tractions and stress fibers control cell shape and rearrangements in collective cell migration
Key to collective cell migration is the ability of cells to rearrange their
position with respect to their neighbors. Recent theory and experiments
demonstrated that cellular rearrangements are facilitated by cell shape, with
cells having more elongated shapes and greater perimeters more easily sliding
past their neighbors within the cell layer. Though it is thought that cell
perimeter is controlled primarily by cortical tension and adhesion at each
cell's periphery, experimental testing of this hypothesis has produced
conflicting results. Here we studied collective cell migration in an epithelial
monolayer by measuring forces, cell perimeters, and motion, and found all three
to decrease with either increased cell density or inhibition of cell
contraction. In contrast to previous understanding, the data suggest that cell
shape and rearrangements are controlled not by cortical tension or adhesion at
the cell periphery but rather by the stress fibers that produce tractions at
the cell-substrate interface. This finding is confirmed by an experiment
showing that increasing tractions reverses the effect of density on cell shape
and rearrangements. Our study therefore reduces the focus on the cell periphery
by establishing cell-substrate traction as a major physical factor controlling
cell shape and motion in collective cell migration.Comment: 39 pages, 6 figure
Coordinated tractions increase the size of a collectively moving pack in a cell monolayer
Cells in an epithelial monolayer coordinate motion with their neighbors
giving rise to collectively moving packs of sizes spanning multiple cell
diameters. The physical mechanism controlling the pack size, however, remains
unclear. A potential mechanism comes from assuming that cell-substrate traction
forces persist over some time scale: with large enough persistence time,
collective cell packs emerge. To test this hypothesis, we measured the velocity
and net traction of each cell. The data showed that in addition to having some
temporal persistence, tractions were spatially correlated, suggesting that
cells coordinate with their neighbors to apply tractions in the same direction.
Chemical inhibitors and activators of actomyosin contraction were used to
determine effects of altering the traction persistence and alignment. Numerical
simulations based on the self-propelled Voronoi model, augmented to include
both traction persistence and alignment and calibrated against the experimental
data, matched the experimentally measured pack size. The model identified that
if there were no alignment of traction between neighboring cells, the size of
the collective pack would be substantially smaller than observed in the
experiments. Hence, combining experiments and a simple mechanical model, this
study confirms the long-standing assumption of traction persistence and adds
the notion of traction alignment between neighbors. Together, persistence and
alignment are two factors controlling the size of a collectively moving cell
pack
Nanoscale Tracking Combined with Cell-Scale Microrheology Reveals Stepwise Increases in Force Generated by Cancer Cell Protrusions
In early breast cancer progression, cancer cells invade through a nanoporous basement membrane (BM) as a first key step toward metastasis. This invasion is thought to be mediated by a combination of proteases, which biochemically degrade BM matrix, and physical forces, which mechanically open up holes in the matrix. To date, techniques that quantify cellular forces of BM invasion in 3D culture have been unavailable. Here, we developed cellular-force measurements for breast cancer cell invasion in 3D culture that combine multiple-particle tracking of force-induced BM-matrix displacements at the nanoscale, and magnetic microrheometry of localized matrix mechanics. We find that cancer-cell protrusions exert forces from picoNewtons up to nanoNewtons during invasion. Strikingly, the protrusions extension involves stepwise increases in force, in steps of 0.2 to 0.5 nN exerted from every 30 s to 6 min. Thus, this technique reveals previously unreported dynamics of force generation by invasive protrusions in cancer cells.Peer reviewe