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Chhabra, T.

Publications and source records attributed to Chhabra, T..

2 recordsLinked to original sources

Glassy dynamics in active epithelia emerge from an interplay of mechanochemical feedback and crowding.

Glassy dynamics in dense epithelial cells remain a subject of debate, as theory predicts its emergence only at unrealistically low cellular activity, yet experimental studies have shown glassy dynamics at physiologically active conditions. In this study, we address this paradox by integrating experimental observations in epithelial monolayers with an active vertex model. We demonstrate that while crowding is essential, it is not sufficient for glassy dynamics to emerge. A mechanochemical feedback loop (MCFL-1), mediated by cell shape changes through the contractile actomyosin network is required to drive glass transition in dense epithelial tissues. Such mechanochemical feedback is captured experimentally via a crosstalk between actin-based cell clustering and dynamic heterogeneity, as well as via force induced actin reorganization in epithelial cells. Incorporating MCFL into the vertex model reveals contrasting results from those previously predicted by theories-we show that the MCFL can counteract cell division-induced fluidisation and enable glassy dynamics to emerge through active cell-to-cell communication. Furthermore, our analysis reveal, for the first time, the existence of novel collective mechanochemical oscillations that arise from the crosstalk of MCFL-1 with oscillatory MCFL-2, capturing ERK mediated cell shape changes. Together, we demonstrate that an interplay between crowding and active mechanochemical feedback enables the emergence of glass-like traits and collective biochemical oscillations in epithelial tissues with active cell-to-cell contacts.

biophysics↗

Differential interfacial tension between oncogenic and wild-type populations forms the mechanical basis of tissue-specific oncogenesis in epithelia

Why does the same oncogenic mutation drive tumor formation in some tissues but not in others? While cancer driver mutations are well-documented, their tissue-specific effects remain largely attributed to genetic factors, leaving the biophysical aspects underexplored. Here, we demonstrate that mechanical interactions, specifically interfacial tension between newly transformed and wildtype epithelial cells are critical in determining survival and growth of HRasV12 oncogenic mutants in human mammary and bronchial epithelia, leading to contrasting outcomes in the two tissues. In mammary epithelium, isolated oncogenic cells are extruded-a typical mechanism of defense against cancer in epithelia-while oncogenic groups become spatially confined in a kinetically arrested, jammed state, marked by an actomyosin belt at the interface. In contrast, bronchial epithelium permits persistent spreading of the same oncogenic cells, which form long protrusions regardless of colony size. Furthermore, oncogenic clusters in these two tissues exhibit distinct biophysical properties, including variations in cell shapes, intracellular pressure, cell-cell tension, and cellular motility. Using a cell shape-tension coupled bi-disperse vertex model, we reveal that differences in interfacial tension at mutant-wild-type boundaries dictate whether oncogenic cells are eliminated, restrained, or expanded and that modulating the heterotypic interfacial tension alters mutant cell fate within the epithelium. Together, our findings uncover a mechanical basis for tissue-specific oncogenesis by highlighting how differential cellular mechanics at the oncogenic-host cell interface regulate tumor initiation and progression.

biophysics↗