Bursts of activity in collective cell migration

Chepizhko, Oleksandr; Giampietro, Costanza; Mastrapasqua, Eleonora; Nourazar, Mehdi; Ascagni, Miriam; Sugni, Michela; Fascio, Umberto; Leggio, Livio; Malinverno, Chiara; Scita, Giorgio; Santucci, Stéphane; Alava, Mikko J.; Zapperi, Stefano; Porta, Caterina A. M. La

doi:10.1073/pnas.1600503113

Cited by 49 publications

(52 citation statements)

References 45 publications

(68 reference statements)

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“…[41] Traditional manual-tracking of individual cells confirmed the reliability of PIV analysis. Thus, PIV has been widely used in quantify and visualize collective cell migration [14,28–31]. Visualization of cell sheet movement using PIV revealed striking propagation of a directionality wave from the leading edge cells to the inside of the cell sheet (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Particle Image Velocimetry (PIV) is a cross-correlation technique initially developed in the field of hydrodynamics, which has been proven to be a useful tool for characterizing local displacements and has been used to study velocity dynamics in collective cell migration [28–31]. To investigate the transmission of directional movement signals from the free edge into a large sheet of corneal epithelial cells, we used PIV to quantitatively analyze and visualize collective cell migration with the detailed distinction between directionality and speed.…”

Section: Introductionmentioning

confidence: 99%

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Collective cell migration has distinct directionality and speed dynamics

Zhang

Lee

et al. 2017

Cell. Mol. Life Sci.

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When a constraint is removed, confluent cells migrate directionally into the available space. How the migration directionality and speed increase are initiated at the leading edge and propagate into neighboring cells are not well understood. Using a quantitative visualization technique — Particle Image Velocimetry (PIV) — we revealed that migration directionality and speed had strikingly different dynamics. Migration directionality increases as a wave propagating from the leading edge into the cell sheet, while the increase in cell migration speed is maintained only at the leading edge. The overall directionality steadily increases with time as cells migrate into the cell-free space, but migration speed remains largely the same. A Particle-Based Compass (PBC) model suggests cellular interplay (which depends on cell-cell distance) and migration speed are sufficient to capture the dynamics of migration directionality revealed experimentally. Extracellular Ca2+ regulated both migration speed and directionality, but in a significantly different way, suggested by the correlation between directionality and speed only in some dynamic ranges. Our experimental and modeling results reveal distinct directionality and speed dynamics in collective migration, and these factors can be regulated by extracellular Ca2+ through cellular interplay. Quantitative visualization using PIV and our PBC model thus provide a powerful approach to dissect the mechanisms of collective cell migration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Collective cell migration has distinct directionality and speed dynamics

Zhang

Lee

et al. 2017

Cell. Mol. Life Sci.

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“…This striking symmetry breaking is in stark contrast with the known isotropic dewetting of passive fluids [45][46][47] . Although pinning of the contact line [46][47][48] may contribute to breaking the radius island that loses its circular symmetry during dewetting, as shown by its contour (red line). Scale bar = 30 µm.…”

Section: Active Forces Govern Tissue Morphology During Dewettingmentioning

confidence: 99%

Active wetting of epithelial tissues

et al. 2018

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Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behavior of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between two-dimensional epithelial monolayers and three-dimensional spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic lengthscale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting — a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumor progression.

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“…The method is based on the comparison of the intensity fields of two consequent photographs of cells. The difference in the intensity is converted into velocity field measured in px/frames and then converted to µm/h (34). The front position is quantified according to Ref.…”

Section: Wound Healing Assaymentioning

confidence: 99%

Chromatin and Cytoskeletal Tethering Determine Nuclear Morphology in Progerin-Expressing Cells

Lionetti

Bonfanti

Budrikis

et al. 2020

Biophysical Journal

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The nuclear morphology of eukaryotic cells is determined by the interplay between the lamina forming the nuclear skeleton, the chromatin inside the nucleus and the coupling with the cytoskeleton. Nuclear alterations are often associated with pathological conditions as in the Hutchinson-Gilford progeria syndrome (HGPS) where a mutation in the lamin A gene yields an altered form of the protein, named progerin, and an aberrant nuclear shape. Here, we introduce an inducible cellular model of HGPS in HeLa cells where increased progerin expression leads to alterations in the coupling of the lamin shell with cytoskeletal/chromatin tethers as well as with Polycomb-group (PcG) proteins. Furthermore, our experiments show that progerin expression leads to enhanced nuclear shape fluctuations in response to cytoskeletal activity. To interpret the experimental results, we introduce a computational model of the cell nucleus that includes explicitly chromatin fibers, the nuclear shell and the coupling with the cytoskeleton. The model allows us to investigate how the geometrical organization of chromatin-lamin tether affects nuclear morphology and shape fluctuations. In sum, our findings highlight the crucial role played by lamin-chromatin and lamin-cytoskeletal alterations in determining nuclear shape morphology and in affecting cellular functions and gene regulation. SIGNIFICANCE Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease characterized by accelerated aging due to a mutation of the lamin A gene, leading to an aberrant protein -named progerin -and to the formation of nuclear blebs. We combine experiments on a cellular model reproducing HGPS cells and numerical simulations of nuclear mechanics to study the biological and biophysical effects of progerin expression on nuclear morphology and functioning. Our results show that progerin induces key changes in the mechanical tethering between cytoskeleton, lamins and chromatin producing nuclear shape alterations and affecting gene regulation.

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Bursts of activity in collective cell migration

Cited by 49 publications

References 45 publications

Collective cell migration has distinct directionality and speed dynamics

Collective cell migration has distinct directionality and speed dynamics

Active wetting of epithelial tissues

Chromatin and Cytoskeletal Tethering Determine Nuclear Morphology in Progerin-Expressing Cells

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