A numerical model suggests the interplay between nuclear plasticity and stiffness during a perfusion assay

Abstract

Cell deformability is a necessary condition for a cell to be able to migrate, an ability that is vital both for healthy and diseased organisms. The nucleus being the largest and stiffest organelle, it often is a barrier to cell migration. It is thus essential to characterize its mechanical behaviour. First, we numerically investigate the visco-elasto-plastic properties of the isolated nucleus during a compression test. This simulation highlights the impact of the mechanical behaviour of the nuclear lamina and the nucleoplasm on the overall plasticity. Second, a whole cell model is developed to simulate a perfusion experiment to study the possible interactions between the cytoplasm and the nucleus. We analyze and discuss the role of the lamina for a wild-type cell model, and a lamin-deficient one, in which the Young's modulus of the lamina is set to 1% of its nominal value. This simulation suggests an interplay between the cytoplasm and the nucleoplasm, especially in the lamin-deficient cell, showing the need of a stiffer nucleoplasm to maintain nuclear plasticity.

In silico approach to quantify nucleus self-deformation on micropillared substrates

“…In line with our previous works (Allena and Aubry 2012;Deveraux et al 2017), we propose a continuum finite elements model to simulate cell behaviour over the flat and micropatterned substrates coated with adhesive fibronectin. As mentioned above, our main objective is to depict the nucleus self-deformation as a function of the micropillared substrate geometry and the actin network around the nucleus itself.…”

“…The contact force f ct automatically applies once the cell approaches the substrate, whether it is flat or micropillared, over a very thin layer corresponding to the superposition between the cell and the substrate. Then, it is approximated by a volume force as proposed in our previous work (Deveraux et al 2017). We employ here a penalization technique via the level set functions g flat and g mp which allow to measure the distance and the interpenetration between the cell and the substrates.…”

“…As previously mentioned (Sect. 2.2.3), the contact force f ct is approximated by a volume force over a very thin layer (Deveraux et al 2017). In fact, by similarity with shell theory, the surface integral in Eq.…”

Fluid shear stress coupled with narrow constrictions induce cell type-dependent morphological and molecular changes in SK-BR-3 and MDA-MB-231 cells

“…Overall, our data regarding both cell dynamics at very short scale and final cell morphology after passing through the constrictions raises the issue of the link between nuclear stiffness and plasticity. Recent experimental 29 and modeling 30 studies have shown that softer nuclei (i.e. Lamin A/C-deficient nuclei in the work of Cao et al) present a larger irreversible plastic deformation after being constricted than stiffer nuclei.…”

Stress fiber anisotropy contributes to force-mode dependent chromatin stretching and gene upregulation in living cells

“…To be consistent with the observed values in live cell experiments, length, width, and thickness of the cell were chosen to be 40, 12, and 8 μm, respectively, and the bead embedding was set to be 38%, as the experimentally measured bead embedding was 36.3% (Supplementary Table 2). The thickness of cell membrane cortex 42 was set to be 0.25 μm. The nucleus was modeled as an elastic ellipsoid with its long axis as 12 μm and short axis as 7 μm.…”