Biology subjects

Monfared, S.

Publications and source records attributed to Monfared, S..

4 recordsLinked to original sources

bioRxiv2026

Mechanical Tension Actively Triggers RhoA-Mediated Cell Extrusion

Cell extrusion is a fundamental process in tissue homeostasis, morphogenesis, and cancer progression, facilitating the removal of cells either alive or through apoptosis. While biochemical signaling pathways are known to regulate extrusion, recent advances have underscored the importance of mechanical forces in this process. Here, using optogenetic control of RhoA activation in epithelial monolayers combined with Bayesian Inversion Stress Microscopy (BISM) and three-dimensional cell-based modeling, we uncover a counterintuitive mechanism whereby elevated tension, instead of stabilizing the monolayer, actively drives extrusion in highly contractile cells. We show that local RhoA activation enhances myosin II-dependent contractility and F-actin reorganization, which promotes cell stiffening, resulting in localized tension buildup. The ensuing tensile stress amplifies vertical mechanical fluctuations, which in turn trigger cell extrusion. Remarkably, these tension-induced extrusions occur both apically and basally. Furthermore, our findings show that RhoA-mediated contractility is not merely an effector of extrusion but also an active promoter of basal extrusion, independently of caspase activation. Our study demonstrates that tensile stress can directly initiate extrusion events and bias their outcome toward apical or basal fates. By identifying tension as a driver rather than a suppressor of extrusion, this work revises current models of epithelial homeostasis and highlights mechanical control as a targetable axis in disease and regeneration.

cell biology↗

bioRxiv2024

Force transmission is a master regulator of mechanical cell competition

Cell competition is a tissue surveillance mechanism for eliminating unwanted cells and as such is indispensable in development, infection and tumorigenesis. Although different biochemical mechanisms are proposed, due to the dearth of direct force measurements, how mechanical forces determine the competition outcome remains unclear. Here, using ex vivo tissues and different cell lines, we have discovered an unknown form of cell competition that is regulated by differences in force transmission capabilities, favoring cell types with stronger intercellular adhesion. Direct force measurements reveal increased mechanical activity at the interface of the two competing cell types in the form of large stress fluctuations which can lead to upward forces and cell elimination. We show how a winning cell type endowed with a stronger intercellular adhesion exhibits a higher resistance to elimination while benefiting from efficient force transmission to neighboring cells. This cell elimination mechanism could have broad implications of keeping strong force transmission ability for maintaining tissue boundaries and cell invasion pathology.

biophysics↗

bioRxiv2024

The Tailtag System: Tracking Multiple Mice in a Complex Environment Over a Prolonged Period Using ArUco Markers.

Despite recent advancements, safely and reliably tracking individual movements over extended periods, particularly within complex social groups, remains challenging. Traditional methods like colour coding, tagging, and RFID tracking, while effective, have notable practical limitations. State-of-the-art neural network-based trackers often struggle to maintain individual identities in large groups for more than a few seconds. Fiducial tags like ArUco codes present a potential solution by enabling accurate tracking and identity management, yet their topical application on mammals has proven difficult without frequent human intervention. In this study, we introduce the Tailtag system: a non-invasive, ergonomic tail ring embedded with an ArUco marker. This system includes a comprehensive parameter optimization guide along with practical guidelines on marker selection. Our Tailtag system demonstrated the ability to automatically and reliably track individual mice in social colonies of up to 20 individuals over a period of seven days without performance degradation, facilitating a detailed analysis of social dynamics in naturalized environments.

animal behavior and cognition↗

bioRxiv2021

Mechanics of live cell elimination

Cell layers eliminate unwanted cells through the extrusion process, which underlines healthy versus flawed tissue behaviors. Although several biochemical pathways have been identified, the underlying mechanical basis including the forces involved in cellular extrusion remain largely unexplored. Utilizing a phase-field model of a three-dimensional cell layer, we study the interplay of cell extrusion with cell-cell and cell-substrate interactions, in a monolayer. Independent tuning of cell-cell versus cell-substrate adhesion forces in the model reveals that a higher cell-substrate adhesion leads to a lower number of total extrusion events. We find extrusion events to be linked to both half-integer topological defects in the orientation field of the cells and to five-fold disclinations in cellular arrangements. We also show that increasing the relative cell-cell adhesion forces translates into a higher likelihood for an extrusion event to be associated with a five-fold disclination and a weaker correlation with +1/2 topological defects. We unify our findings by accessing mechanical stress fields: an extrusion event acts as a mechanism to relieve localized stress concentration.

biophysics↗