Biology subjects

d'Alessandro, J.

Publications and source records attributed to d'Alessandro, J..

4 recordsLinked to original sources

bioRxiv2026

Vimentin bridges scales to convert polarized cell locomotion into coordinated collective migration

Collective cell migration is central in development and disease. Vimentin is an intermediate filament protein expressed by epithelial cells at the edge of wounds where collective cell migration is most efficient. Yet, its functional role in this context remains underexplored. Here, we show that vimentin, over-expressed in cells undergoing partial epithelial to mesenchymal transition at the edge of epithelial monolayers, has a multiscale impact on the whole monolayer mechano-dynamics. Vimentin knock-down delays wound closure, reduces cell coordination, while increasing traction forces exerted by cells on the substratum. It also disrupts the directionality of leader cells migration, as well as the cohesion and coordinated motion of cells deep in the monolayer. We further show that vimentin promotes the conversion of polarized cell locomotion into coordinate collective migration by polarizing actin, focal adhesions and traction forces, sustaining leader cells lamellipodium protrusive activity and directionality, while allowing mechanical coupling of leader with follower cells. Altogether, we show that vimentin is essential for bridging polarized single cell locomotion and coordinated collective migration to allow efficient collective migration. Significant statementEpithelial cells migrate coordinately to repair tissue. Vimentin, transiently enriched at the wound edge plays a key role in guiding this process by converting polarized cell locomotion into coordinate collective migration, enabling leader cells to polarize, form stable protrusions, and maintain directed migration, while allowing mechanical coupling of front cells with followers, necessary for efficient coordinated collective migration. These findings reveal vimentin, a known EMT marker, as a novel positive regulator of efficient wound healing.

cell biology↗

bioRxiv2022

Microphase separation of living cells

Self-organization of cells is central to a variety of biological systems and physical concepts of condensed matter have proven instrumental in deciphering some of their properties. Here we show that microphase separation, long studied in polymeric materials and other inert systems, has a natural counterpart in living cells. When placed below a millimetric film of liquid nutritive medium, a quasi two-dimensional, high-density population of Dictyostelium discoideum cells spontaneously assemble into compact domains. Their typical size of 100 m is governed by a balance between competing interactions: an adhesion acting as a short-range attraction and promoting aggregation, and an effective long-range repulsion stemming from aerotaxis in near anoxic condition. Experimental data, a simple model and cell-based simulations all support this scenario. Our findings establish a generic mechanism for self-organization of living cells and highlight oxygen regulation as an emergent organizing principle for biological matter.

biophysics↗

bioRxiv2021

Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration

Cell dispersion from a confined area is fundamental in a number of biological processes, including cancer metastasis. To date, a quantitative understanding of the interplay of single cell motility, cell proliferation, and intercellular contacts remains elusive. In particular, the role of E- and N-Cadherin junctions, central components of intercellular contacts, is still controversial. Combining theoretical modeling with in vitro observations, we investigate the collective spreading behavior of colonies of human cancer cells (T24). Inhibition of E- and N-Cadherin junctions decreases colony spreading and average spreading velocities, without affecting the strength of correlations in spreading velocities of neighboring cells. Based on a biophysical simulation model for cell migration, we show that the behavioral changes upon disruption of these junctions can be explained by reduced repulsive excluded volume interactions between cells. This suggests that cadherin-based intercellular contacts sharpen cell boundaries leading to repulsive rather than cohesive interactions between cells, thereby promoting efficient cell spreading during collective migration.

biophysics↗

bioRxiv2018

Sustained oscillations of epithelial cell sheets

Morphological changes during development, tissue repair, and disease largely rely on coordinated cell movements and are controlled by the tissue environment. Epithelial cell sheets are often subjected to large scale deformation during tissue formation. The active mechanical environment in which epithelial cells operate have the ability to promote collective oscillations, but how these cellular movements are generated and relate to collective migration remains unclear. Here, combining in vitro experiments and computational modelling we describe a novel mode of collective oscillations in confined epithelial tissues where the oscillatory motion is the dominant contribution to the cellular movements. We show that epithelial cells exhibit large-scale coherent oscillations when constrained within micro-patterns of varying shapes and sizes, and that their period and amplitude are set by the smallest confinement dimension. Using molecular perturbations, we then demonstrate that force transmission at cell-cell junctions and its coupling to cell polarity are pivotal for the generation of these collective movements. We find that the resulting tissue deformations are sufficient to trigger mechanotransduction within cells, potentially affecting a wide range of cellular processes.

biophysics↗