Abstract: |
The cellular nucleus is enclosed by a permeable membrane mechanically supported by a meshwork of lamin fibers. The morphology and integrity of the nucleus are essential for the cell`s function. Recent experiments show that loss of the lamin network results in nuclear deformations and rupture. To understand the mechanistic basis of this phenomenon, we developed a mathematical model that accounts for, and couples, the fluid flows around and through the permeable membrane, and the pulling on the membrane by membrane-bound, but mobile, molecular motors attached to impinging microtubules. Here the microtubules are assumed to nucleate from a cellular centrosome. We found that this model predicts the formation of a sharp corner in the vicinity of the centrosome, rather reminiscent of the Taylor cone for a surfactant-laden drop in an elongational flow. We analyze the equilibrium shape of the membrane in terms of the total number of motors and their mobility in the nuclear membrane. Our model provides a more mechanistic understanding of nuclear deformation in cells and can give insights into the correspondence between motor forces and membrane deformation leading to nuclear rupture, which has been observed in some cancer cells. Using numerical simulations we further investigate how the distribution of molecular motors couples to the deformation and shape dynamics of the nucleus. |
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