Biology subjects

Versaevel, M.

Publications and source records attributed to Versaevel, M..

3 recordsLinked to original sources

bioRxiv2026

Geometric confinement regulates ERK signaling dynamics and collective migration

Collective cell migration is a fundamental process in morphogenesis, tissue repair, cancer invasion, and frequently occurs under geometric confinement in vivo. However, how confinement interfaces with signaling pathways that coordinate collective motion remains poorly understood. Here, we confine migrating epithelial monolayers within adhesive microstripes of defined width and observe a progressive slow-down of collective migration with increasing spatial confinement. Combining biophysical modeling, live imaging of ERK activity, and pharmacological perturbations, we show that confinement increases tissue crowding while reducing cell and nuclear projected areas, thereby shifting epithelial tissues toward a mechanically compressed state associated with dampened ERK waves. Across conditions, migration speed scales with ERK signaling dynamics, which correlates with EGFR signaling as well as cell and nuclear projected areas, together serving as quantitative proxies for the confinement-imposed mechanical state. Pharmacological inhibition of ROCK restores cell spreading, ERK signaling, and migration under strong confinement, demonstrating that this state is reversible and governed by actomyosin contractility. Together, our results identify geometric confinement as a physical regulator of a contractility-dependent mechanochemical state that controls ERK signaling and collective migration in epithelial tissues.

biophysics↗

bioRxiv2024

Matrix viscoelasticity controls epithelial cell mechanobiology through dimensionality

In recent years, matrix viscoelasticity has emerged as a potent regulator of fundamental cellular processes and has been implicated in promoting cancer progression. Alongside viscoelasticity, additional ECM cues have been shown to influence migration decision-making of cancer cells, and spatial confinement is now considered as a potential regulator of metastasis. However, our understanding of these complex processes predominantly relies on purely elastic hydrogels, and the exact relationship between matrix viscoelasticity and spatial confinement in driving epithelial cell mechanotransduction and migration during cancer progression remains unclear. Here, we systematically investigated the interplay between matrix stiffness, viscoelasticity and spatial confinement by engineering soft ([~]0.3 kPa) and stiff ([~]3 kPa) polyacrylamide hydrogels with varying degrees of viscous dissipation, mirroring the mechanical properties of healthy and tumoral conditions in breast tissue. We observed that viscoelasticity modulates cell spreading, focal adhesions and YAP nuclear import in opposite directions on soft and stiff substrates. Strikingly, viscoelasticity enhances migration speed and persistence on soft substrates, while impeding them on stiff substrates via actin retrograde flow regulation. Combining soft micropatterning with viscoelastic hydrogels, we also show that spatial confinement restricts cell migration on soft matrices regardless of matrix viscoelasticity and promotes migration on stiff matrices in a viscoelasticity-dependent fashion. Our findings establish substrate viscoelasticity as a key regulator of epithelial cell functions and unravel the role of the matrix dimensionality in this process. SignificanceWhile matrix elasticity has received significant attention, recent findings underscore the importance of its natural dissipative properties and spatial confinement in regulating cellular processes and tumour invasiveness. However, the intricate interplay between viscoelasticity and spatial confinement in orchestrating epithelial cell behaviour during cancer progression remains elusive. Using micropatterned viscoelastic hydrogels to replicate the mechanical properties encountered during breast tumour progression, we unveil that viscoelasticity modulates cell behaviour and mechanotransduction signals differently on soft and stiff substrates. Increased viscoelasticity enhances migration speed and persistence on soft substrates while impeding them on stiff substrates via actin retrograde flow regulation. Furthermore, spatial confinement restricts cell migration on soft matrices regardless of viscoelasticity, while promoting migration on stiff matrices in a viscoelasticity-dependent manner.

biophysics↗

bioRxiv2022

Mechanoresponse of epithelial monolayers to in-plane and out-of-plane curvatures imposed by 3D microwells

The organization of epithelial tissues with precise spatial definition is essential to various biological processes and to generate curved epithelial structures. However, the regulation of the architecture and dynamics of collective epithelial assemblies by the matrix curvature remains understudied. Here, we photopolymerize microwells of various diameters in hydrogels to form curved epithelial structures such as breast epithelial lobules, and study how in-plane and out-of-plane curvatures modulate the mechanoresponse of epithelial tissues. In-plane curvature governed by the microwell radius drives the centripetal orientation of cells and nuclei close to the edge of the microwell, resulting from contractile forces exerted by a supracellular actomyosin purse-string. Convex out-of-plane curvature imposed at the microwell entrance leads to a vertical orientation of the nuclei towards the microwell axis. We demonstrated that increasing the out-of-plane curvature leads to more flatten and elongated nuclear morphologies with high levels of compacted chromatin. Epithelial cells exhibit higher directionality and speed around the microwell edge, demonstrating that the out-of-plane curvature significantly enhances the cellular trafficking. These findings demonstrate the importance of in-plane and out-of-plane curvatures in epithelial organization and how both can be leveraged to facilitate the engineering of curved structures to study curvature-dependent mechanotransduction pathways.

biophysics↗