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Model of T-Cell Nuclear Deformation by the Cortical Actin Layer
Authors:Gur Fabrikant  Soumya Gupta  GV Shivashankar  Michael M Kozlov
Institution: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel; Mechanobiology Institute and Department of Biological Sciences, National University of Singapore, Singapore
Abstract:Deformations of cell nuclei accompany a number of essential intracellular processes. Although evidence is being accumulated on the primary role actin structures play in controlling the shape of the nucleus, the mechanisms behind this phenomenon remain unknown. Here, we consider theoretically a specific paradigm of nuclear deformation, and a related actin rearrangement, in T cells stimulated by contact with a bead covered by surrogate antigens. We suggest that the nucleus is deformed by the elastic forces developed within a cylindrical layer of polymerized actin, which is generated as a result of the receptor-mediated T-cell activation. We substantiate this proposal with a theoretical analysis of mutual deformations in the actin layer and the nucleus, which recovers the experimentally observed nuclear shapes. Furthermore, we evaluate the forces developed by the actin polymerization that drives the nuclear deformation. The model predicts the mode of actin polymerization generated by the surrogate antigens covering a bead and the values of the elastic moduli of the nuclear shell. We provide a qualitative experimental support for the model assumptions by visualizing the stages of nuclear shape change and the corresponding evolution of the cortical actin.
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