In the stationary epithelium, the Golgi apparatus assumes an apical position, above the cell nucleus. However, during wound healing and morphogenesis, as the epithelial cells start migrating, it relocalizes closer to the basal plane. On this plane, the position of Golgi with respect to the cell nucleus defines the organizational polarity of a migrating epithelial cell, which is crucial for an efficient collective migration. Yet, factors influencing the Golgi polarity remain elusive. Here, we constructed a graph neural network-based deep learning model to systematically analyze the dependency of Golgi polarity on multiple geometric and physical factors. In spite of the complexity of a migrating epithelial monolayer, our simple model was able to predict the Golgi polarity with 75% accuracy. Moreover, the model predicted that Golgi polarity predominantly correlates with the orientation of maximum principal stress. Finally, we found that this correlation operates locally since progressive coarsening of the stress field over multiple cell-lengths reduced the stress polarity-Golgi polarity correlation as well as the predictive accuracy of the neural network model. Taken together, our results demonstrate that graph neural networks could be a powerful tool toward understanding how different physical factors influence collective cell migration. They also highlight a previously unknown role of physical cues in defining the intracellular organization.
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http://dx.doi.org/10.1159/000528354 | DOI Listing |
Lab Chip
January 2025
Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland.
A novel microfluidic platform was designed to study the cellular architecture of endothelial cells (ECs) in an environment replicating the 3D organization and flow of blood vessels. In particular, the platform was constructed to investigate EC defects in slow-flow venous malformations (VMs) under varying shear stress and flow conditions. The platform featured a standard microtiter plate footprint containing 32 microfluidic units capable of replicating wall shear stress (WSS) in normal veins and enabling precise control of shear stress and flow directionality without the need for complex pumping systems.
View Article and Find Full Text PDFFront Cell Dev Biol
January 2025
Department of Biomedical Sciences (DSB), Institute of Experimental Endocrinology and Oncology "G. Salvatore" (IEOS), National Research Council (CNR), Naples, Italy.
The GC (Golgi complex) plays a pivotal role in the trafficking and sorting of proteins and lipids until they reach their final destination. Additionally, the GC acts as a signalling hub to regulate a multitude of cellular processes, including cell polarity, motility, apoptosis, DNA repair and cell division. In light of these crucial roles, the GC has garnered increasing attention, particularly given the evidence that a dysregulation of GC-regulated signalling pathways may contribute to the onset of various pathological conditions.
View Article and Find Full Text PDFCell Rep
January 2025
Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address:
Cytotoxic immune cells mediate precise attacks against diseased cells to maintain organismal health. Their operational unit of killing and host defense is lytic granules (LGs), which are specialized lysosomal-related organelles. Precision in cytotoxicity is achieved by converging the many LGs to the microtubule-organizing center (MTOC) and polarizing these to the diseased cell for secretion.
View Article and Find Full Text PDFMol Biol Cell
January 2025
Department of Biology, The Catholic University of America, Washington, DC, 20064.
MAL2 (myelin and lymphocyte protein 2) and rab17 have been identified as hepatocellular carcinoma tumor suppressors. However, little is known how their functions in hepatic polarized protein sorting/trafficking translates into how they function in the epithelial to mesenchymal transition and/or the mesenchymal to epithelial transition in metastases. To investigate this, we expressed MAL2 and rab17 alone or together in hepatoma-derived Clone 9 cells (that lack endogenous MAL2 and rab17).
View Article and Find Full Text PDFJ Microsc
January 2025
Biotechnology of Natural Products, TUM School of Life Sciences, Technical University of Munich, Munich, Germany.
Until recently, the lack of three-dimensional visualisation of whole cells at the electron microscopic (EM) level has led to a significant gap in our understanding of the interaction of cellular organelles and their interconnection. This is particularly true with regard to the role of the endoplasmic reticulum (ER). In this study, we perform three-dimensional reconstructions of serial FIB/SEM stacks and anaglyphs derived from volume rendering, cryo-scanning electron microscopy (cryo-SEM) and state-of-the-art electron microscopy immobilisation and imaging techniques.
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