Biology subjects

Atia, L.

Publications and source records attributed to Atia, L..

5 recordsLinked to original sources

bioRxiv2026

Local mechanical gradients underlie coordinated cascades of epithelial cell-cycle advance

Cell division mechanically perturbs the local environment in epithelial tissues, yet whether and how these perturbations propagate to coordinate cell-cycle progression across neighboring cells remains unclear. Here, we combine live cell-cycle tracking with mechanical analysis to examine how division events organize in space and time. We find that coordinated changes and spatial gradients in forces, morphology, and dynamics precede synchronized G1[->]S transitions in nearby cells. These transitions emerge within localized high-tension zones and give rise to spatiotemporal clusters of cell divisions, indicating that division events are mechanically coupled and propagate across neighboring cells. Supporting this biophysical picture, similar mechanical patterns arising from cell extrusion are sufficient to induce cell-cycle re-entry in neighboring cells. Together, these findings suggest a mechanically mediated framework for coordinated proliferation, possibly driven by positive mechanical feedback.

biophysics↗

bioRxiv2026

IPF AT2 cells are stuck in transition and biophysically dysfunctional

Idiopathic Pulmonary Fibrosis (IPF) is an incurable disease with extensive molecular, cellular, and organ level dysfunction. A major gap in IPF research is the lack of understanding of how short-term cellular behavior causes long-term tissue remodeling. By optimizing lung slices from explanted human lungs, we discovered foci of migratory non-canonical alveolar type 2 (AT2) cells in regions of established lung fibrosis and found that these cells are trapped in states of cellular transition that are driven by persistent developmental repair programs. Consistent with these biophysical behaviors, pharmacological activation of {beta}-catenin reproduced persistent migration, whereas YAP activation restrained it. We conclude that imbalanced developmental programs drive AT2 cell motility and lesion heterogeneity, providing a mechanistic link between short-term cellular dynamics and slowly progressive fibrosis of IPF.

cell biology↗

bioRxiv2025

3D-printed toolkit for regulating epithelial unjamming

During wound healing and cancer invasion, epithelial monolayers transition from a solid-like, jammed state to a fluid-like unjammed state. However, affordable and accessible tools for modeling and precise tuning of this response remain limited. Here, we present a simple, lithography-free 3D-printed toolkit of customizable inserts and scratchers for fabricating micro-gaps with defined geometries and widths down to [~]50 {micro}m, without requiring cleanroom facilities or specialized expertise. Using epithelial monolayers, we demonstrate that gap width fundamentally regulates unjamming dynamics. Narrow gaps induced rapid, coordinated migration with high initial velocities, whereas wide gaps suppressed early unjamming and produced slower, spatially heterogeneous closure. Cell shape dynamics confirmed conserved elongation, cell rounding, and closure behaviors across conditions. The presented toolkit provides new opportunities for investigating the mechanical and molecular mechanisms that regulate epithelial plasticity, enabling fine control of unjamming transitions and allowing the modeling of both healthy and pathological wound-response regimes.

biophysics↗

bioRxiv2023

ConfluentFUCCI for fully-automated analysis of cell-cycle progression in a highly dense collective of migrating cells

Understanding mechanisms underlying various physiological and pathological processes requires accurate and fully automated analysis of dense cell populations that collectively migrate, and specifically, relations between biophysical features and cell cycle progression aspects. A seminal tool that led to a leap in real-time study of cell cycle is the fluorescent ubiquitination-based cell cycle indicator (FUCCI). Here, we introduce ConfluentFUCCI, an open-source graphical user interface-based framework designed for fully automated analysis of cell cycle progression, cellular dynamics, and cellular morphology, in highly dense migrating cell collectives. Leveraging state-of-the-art tools, some incorporate deep learning, ConfluentFUCCI offers accurate nuclear segmentation and tracking using FUCCI tags, enabling comprehensive investigation of cell cycle progression at both the tissue and single-cell levels. We compare ConfluentFUCCI to the most recent relevant tool, showcasing its accuracy and efficiency in handling large datasets. Furthermore, we demonstrate the ability of ConfluentFUCCI to monitor cell cycle transitions, dynamics, and morphology within densely packed epithelial cell populations, enabling insights into mechanotransductive regulation of cell cycle progression. The presented tool provides a robust approach for investigating cell cycle-related phenomena in complex biological systems, offering potential applications in cancer research and other fields.

cell biology↗

bioRxiv2018

The tumor suppressor p53 promotes carcinoma invasion and collective cellular migration

SummaryLoss of function of the tumor suppressor p53 is generally thought to increase cell motility and invasiveness. Using 2-D confluent and 3-D spheroidal cell motility assays with bladder carcinoma cells and colorectal carcinoma cells, we report, to the contrary, that loss of p53 can decrease cell motility and invasion.\n\nAbstractFor migration of the single cell studied in isolation, loss of function of the tumor suppressor p53 is thought to increase cell motility. Here by contrast we used the 2-D confluent cell layer and the 3-D multicellular spheroid to investigate how p53 impacts dissemination and invasion of cellular collectives. We used two human carcinoma cell lines, the bladder carcinoma EJ and the colorectal carcinoma HCT116. We began by replicating single cell invasion in the traditional Boyden chamber assay, and found that the number of invading cells increased with loss of p53, as expected. In the confluent 2-D cell layer, however, for both EJ and HCT, speeds and effective diffusion coefficients for the p53 null types compared to their p53 expressing counterparts were significantly smaller. Compared to p53 expressers, p53 null cells exhibited more organized cortical actin rings together with reduced front-rear cell polarity. Furthermore, loss of p53 caused cells to exert smaller traction forces upon their substrates, and reduced formation of cryptic lamellipodia. In a 3-D collagen matrix, p53 consistently promoted invasion of the multicellular spheroids into surrounding matrix. Together, these results show that p53 expression in these carcinoma model systems increases collective cellular migration and invasion. As such, these studies point to paradoxical contributions of p53 in single cell versus collective cellular migration.

cancer biology↗