Abstract Cell migration is orchestrated by a complicated mechanochemical system. However, few cell migration models take account of the coupling between a biochemical network and mechanical factors. Here, we construct a mechanochemical cell migration model to study the cell tension effect on cell migration. Our model incorporates the interactions between Rac-GTP, Rac-GDP, F-actin, myosin, and cell tension, and it is based on phase field approach hence very convenient in describing the cell shape change. This model captures common features of cell polarization, cell shape change, and cell migration modes. It shows cell tension inhibits migration ability monotonically when cells are applied with persistent external stimuli. On the other hand, if random internal noise is significant, the regulation of cell tension exerts a non-monotonic effect on cell migration. As the elevation of cell tension impedes the formation of multiple protrusions hence enhances the streamline position of the cell body. Therefore the migration ability could be maximized at intermediate cell tension under random internal noise. These model predictions are consistent with our singlecell experiments and other experimental results. Statement of significance Cell migration plays a vital role in many biological processes such as tumor metastasis. It is a complicated process regulated by dynamic coupling between the biochemical network and mechanical forces. However, few cell migration models take account of both factors. Here, we construct a mechanochemical cell migration model to study how cell migration is regulated by cell tension. Our model predicts that cell tension not only inhibits cell movement under persistent external stimuli but also prompts cell migration under random internal noise when cell tension is low. Therefore an optimized cell tension could maximize the migration ability under random internal noise. We further confirmed these model predictions are consistent with our single-cell experiments and other published experimental results.
Therapeutic irradiation for head and neck cancer, and the autoimmune disease Sjögren's syndrome, lead to loss of salivary parenchyma. They are the two main causes of irreversible salivary gland hypofunction. Such patients cannot produce adequate levels of saliva, leading to considerable morbidity. We are working to develop an artificial salivary gland for such patients. A major problem in this endeavor has been the difficulty in obtaining a suitable autologous cellular component. This article describes a method of culturing and expanding primary salivary cells obtained from human submandibular glands (huSMGs) that is serum free and yields cells that are epithelial in nature. These include morphological (light and transmission electron microscopy [TEM]), protein expression (immunologically positive for ZO-1, claudin-1, and E-cadherin), and functional evidence. Under confocal microscopy, huSMG cells show polarization and appropriately localize tight junction proteins. TEM micrographs show an absence of dense core granules, but confirm the presence of tight and intermediate junctions and desmosomes between the cells. Functional assays showed that huSMG cells have high transepithelial electrical resistance and low rates of paracellular fluid movement. Additionally, huSMG cells show a normal karyotype without any morphological or numerical abnormalities, and most closely resemble striated and excretory duct cells in appearance. We conclude that this culture method for obtaining autologous human salivary cells should be useful in developing an artificial salivary gland.
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