3D single cell migration driven by temporal correlation between oscillating force dipoles
- Laboratory of Cell Physics, ISIS/IGBMC, UMR 7104, Inserm, and University of Strasbourg, France
- Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico Chimie Curie, France
- Université Paris-Saclay, CNRS, Laboratoire de l’accélérateur linéaire, France
- Univ. Lyon, Université Claude Bernard Lyon 1, CNRS, France
- Saarland University, Center for Biophysics, Biologische Experimentalphysik, Germany
- Tumor Biomechanics, INSERM UMR S1109, Institut d’Hématologie et d’Immunologie, France
Figures
Figure 1 with 3 supplements
Key players in cell motility.
(a) Left panel (and Video 1): A cell deforms the fibronectin (FN) network when migrating (FN in yellow and mCherry-LifeAct for actin filaments in red). Right panel: Enlargement of the white windows …
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Figure 1—source data 1
CDM characterization.
(i) Values for the height and the thickness of the cell derived matrix (CDM). (ii) Raw values of the CDM’s Young’s modulus. (iii) Values for the cytoplasts’ period of oscillation.
- https://cdn.elifesciences.org/articles/71032/elife-71032-fig1-data1-v2.xlsx
Figure 1—figure supplement 1
Characterization of cell derived matrix (CDM).
(a) Schematics of the CDM preparation. (b) Electron microscope images of the top layer (x−y) and the side view (x−z) of CDM; scale bars 10μm. (c) Cells are embedded in the CDM. Top: schematic; …
Figure 1—figure supplement 2
Cells deform the cell derived matrix (CDM) network.
Fibronectin (FN) in yellow and cell expressing RFP-zyxin, scale bar 25 μm. Right side shows a blow up of one of the zones highlighted by the squares, scale bar 5 μm. White arrows show the movement …
Figure 1—figure supplement 3
Different types of fibroblasts generate contractile-extensile regions on either side of the nucleus in cell derived matrices (CDMs).
(a) Top: Snapshot of mouse embryonic fibroblast (MEF) embedded in a CDM. Scale bar 50 µm. Overlay of phase contrast image and Kanade-Lucas-Tomasi (KLT) calculation of the mesh displacement (green …
Figure 2 with 2 supplements
Dynamics of matrix deformation for migrating and non-migrating cells.
(a) Snapshots overlaying phase contrast images and Kanade-Lucas-Tomasi (KLT) calculation of matrix rate of deformation (green arrows indicate displacement between two consecutive frames, Δt=1 min) …
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Figure 2—source data 1
Matrix contraction.
(i) Raw values for the periods of non-migrating and nocodazole-treated cells. (ii) Raw values for the periods of migrating cells. (iii) Front-back phase shift for migrating and non-migrating cells. (iv) Raw values for the amplitude of the divergence peaks.
- https://cdn.elifesciences.org/articles/71032/elife-71032-fig2-data1-v2.xlsx
Figure 2—figure supplement 1
Analysis pipeline.
(a) Overlay of phase contrast image and Kanade-Lucas-Tomasi (KLT) calculation of mesh displacement (green arrows indicate displacement between two consecutive frames, Δt=1 min) of an NIH3T3 …
Figure 2—figure supplement 2
Divergence amplitudes.
Plot of average divergence amplitudes at front and back of migrating (n=13) and non-migrating cells (n=6), N>3. Migrating: back 0.010±0.005 min–1 and front 0.009±0.005 min–1. Non-migrating: back …
Figure 3 with 3 supplements
Multipole analysis of the matrix deformation rate.
(a) Snapshots of a cell with: matrix rate of deformation, green arrows, the main dipole axis, blue, the axis of the cell motion, red. (b) Schematic representation of dipoles (D) and quadrupoles (Q) …
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Figure 3—source data 1
Dipole and quadrupole moments.
- https://cdn.elifesciences.org/articles/71032/elife-71032-fig3-data1-v2.xlsx
Figure 3—figure supplement 1
Method to compute the multipolar terms.
Figure 3—figure supplement 2
Quantification of cell and dipole orientation.
Histograms of the angle difference between the main dipole axis and the direction of motion (blue and red axes, respectively, in the top-left panel). The full histogram (yellow) is a merge of …
Figure 3—figure supplement 3
Quantification of cell motion.
(a) Examples of cell trajectories represented in the dipole/quadrupole phase space. Comparison between cycle curves obtained in different experiments for different migrating (top panels) and …
Figure 4 with 2 supplements
Persistent speed is related to the period of oscillations.
(a) Schematics of dipoles distribution highlighting quantities used in the theoretical model: two dipolar units (‘A’ and ‘B’) made up of disks of radius a, through which cells exert traction forces …
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Figure 4—source data 1
Persistent speed and period of cell migration trajectories.
(i) Data shown in the panel Figure 4d, persistent speed vs. period. (ii) Persistent speed for WT cells, C8-BPA-treated cells, CK666-treated cells, ML-7-treated cells and Y27632-treated cells. (iii) Period of WT cells, C8-BPA-treated cells, CK666-treated cells, ML-7-treated cells, and Y27632-treated cells. (iv) Dipole and quadrupole moments of simulated cells (migrating and non-migrating).
- https://cdn.elifesciences.org/articles/71032/elife-71032-fig4-data1-v2.xlsx
Figure 4—figure supplement 1
Cell motion in cell derived matrix (CDM) is modified in the presence of specific inhibitors.
Typical cell morphologies and typical trajectories of cells migrating over 5 hr. Bright-field and LifeAct labeling. (a) Control (n=49). (b) Blebbistatin (n=31). (c) Y-27632 (n=9). (d) ML-7 (n=24). (e…
Figure 4—figure supplement 2
Simulated cell trajectories in the dipole/quadrupole phase space.
(a) Reproduction of the idealized model of cell dynamics (from Figure 4b) showing alternate phases of dipole contraction/extension at the two cell ends. Sinusoidal oscillations have been chosen in …
Figure 5 with 1 supplement
Cell motion is triggered by means of laser-induced force dipoles.
(a) Schematic of laser ablation experiment. (b) (Left panel: LifeAct, middle panel: phase contrast and KLT, arrows indicate displacement between two consecutive frames, Δt=10 s). Ablation at the …
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Figure 5—source data 1
Cell migration induced by laser ablation.
(i) Migration trajectories of cells which are exposed to laser ablation-induced contractions.
- https://cdn.elifesciences.org/articles/71032/elife-71032-fig5-data1-v2.xlsx
Figure 5—figure supplement 1
Cell motion is triggered by means of laser-induced force dipoles.
(a) Cell expressing mCherry-LifeAct and GFP-NMHC show increased signal following laser cut indicated with white dashed squares. Inset shows region of cut. Scale bar 20 μm (left) and 10 μm (right). (b…
Videos
Video 1
NIH3T3 fibroblast transfected with mCherry-LifeAct deforms the fibronectin network in yellow while moving, scale bar 20 μm, time in hh:mm.
Video 2
Cell derived matrix (CDM) is elastic, as shown by optical tweezer characterization, time in mm:ss.
Video 3
Cells motion in 3D with cell derived matrix (CDM) and the associated focal contacts dynamics fibronectin in yellow and zyxin in red, time in hh:mm:ss.
Video 4
Microtubule asymmetric distribution (left) is associated with cell polarity during motion, time in hh:mm.
Video 5
Cell deforms the cell derived matrix (CDM), time in hh:mm.
Video 6
Formation of myosin clusters simultaneously to contraction, time in mm:ss.
Video 7
Another example of cell motion in cell derived matrix (CDM), scale bar 25 μm, time in hh:mm.
Video 8
Phase shift between local dipoles is associated with cell motion; cell motion (left, LifeAct red), fibronectin network deformation (center yellow), merge, time in hh:mm:ss.
Video 9
Cell motility in the presence of nocodazole added at time 0, time in hh:mm, scale bar 25 μm.
Video 10
Nucleus-free cell forms and shows oscillatory motion in cell derived matrix (CDM).
Time in hh:mm and scale bar 25 μm.
Video 11
Cell motility in the presence of blebbistatin added at time 0, time in hh:mm, scale bar 25 μm.
Video 12
Cell motility in the presence of latrunculin A added at time 0, time in hh:mm, scale bar 25 μm.
Video 13
Local laser ablation triggers the local recruitment of actin and local contraction, time in mm:ss.
Video 14
