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Khuntia, P.

Publications and source records attributed to Khuntia, P..

2 recordsLinked to original sources

Prediction of Golgi Polarity in Collectively Migrating Epithelial Cells Using Graph Neural Network

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 starts 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 demonstrated that graph neural networks could be a powerful tool towards understanding how different physical factors influence collective cell migration. They also highlighted a previously unknown role of physical cues in defining the intracellular organization.

cell biology↗

Mechanosensitive dynamics of lysosomes regulates the emergence of leader cells during collective cell migration

Collective cell migration during embryonic development, wound healing, and cancer metastasis entails the emergence of leader cells at the migration front. These cells with conspicuous lamellipodial structures provide directional guidance to the collective. Despite their physiological relevance, the mechanisms underlying the emergence of leader cells remain elusive. Here we report that in diverse model systems for wound healing, including cultured epithelial monolayer, Drosophila embryo, and mouse embryonic skin, leader cells display a peripheral accumulation of lysosomes. This accumulation appears essential for leader cell emergence, involves lysosomal movement along microtubules, and depends on the actomyosin contractility-generated cellular forces. Peripheral lysosomes associate with inactive Rac1 molecules to remove them from the leading periphery, which increases local Rac1-activity, triggering actin polymerization and promoting lamellipodium formation. Taken together, we demonstrate that beyond their catabolic role, lysosomes act as the intracellular platform that links mechanical and biochemical signals to control the emergence of leader cells.

cell biology↗