Nejvíce citovaný článek - PubMed ID 30029237
A Finite Element Bendo-Tensegrity Model of Eukaryotic Cell
The failure of intracellular zinc accumulation is a key process in prostate carcinogenesis. Although prostate cancer cells can accumulate zinc after long-term exposure, chronic zinc oversupply may accelerate prostate carcinogenesis or chemoresistance. Because cancer progression is associated with energetically demanding cytoskeletal rearrangements, we investigated the effect of long-term zinc presence on biophysical parameters, ATP production, and EMT characteristics of two prostate cancer cell lines (PC-3, 22Rv1). Prolonged exposure to zinc increased ATP production, spare respiratory capacity, and induced a response in PC-3 cells, characterized by remodeling of vimentin and a shift of cell dry mass density and caveolin-1 to the perinuclear region. This zinc-induced remodeling correlated with a greater tendency to maintain actin architecture despite inhibition of actin polymerization by cytochalasin. Zinc partially restored epithelial characteristics in PC-3 cells by decreasing vimentin expression and increasing E-cadherin. Nevertheless, the expression of E-cadherin remained lower than that observed in predominantly oxidative, low-invasive 22Rv1 cells. Following long-term zinc exposure, we observed an increase in cell stiffness associated with an increased refractive index in the perinuclear region and an increased mitochondrial content. The findings of the computational simulations indicate that the mechanical response cannot be attributed exclusively to alterations in cytoskeletal composition. This observation suggests the potential involvement of an additional, as yet unidentified, mechanical contributor. These findings indicate that long-term zinc exposure alters a group of cellular parameters towards an invasive phenotype, including an increase in mitochondrial number, ATP production, and cytochalasin resistance. Ultimately, these alterations are manifested in the biomechanical properties of the cells.
- Klíčová slova
- Actin, Cancer, Cytoskeleton, Mechanobiology, Metabolism, Mitochondria, Vimentin, Zinc,
- Publikační typ
- časopisecké články MeSH
Biomechanical models based on the finite element method have already shown their potential in the simulation of the mechanical behaviour of cells. For instance, development of atherosclerosis is accelerated by damage of the endothelium, a monolayer of endothelial cells on the inner surface of arteries. Finite element models enable us to investigate mechanical factors not only at the level of the arterial wall but also at the level of individual cells. To achieve this, several finite element models of endothelial cells with different shapes are presented in this paper. Implementing the recently proposed bendotensegrity concept, these models consider the flexural behaviour of microtubules and incorporate also waviness of intermediate filaments. The suspended and adherent cell models are validated by comparison of their simulated force-deformation curves with experiments from the literature. The flat and dome cell models, mimicking natural cell shapes inside the endothelial layer, are then used to simulate their response in compression and shear which represent typical loads in a vascular wall. The models enable us to analyse the role of individual cytoskeletal components in the mechanical responses, as well as to quantify the nucleus deformation which is hypothesized to be the quantity decisive for mechanotransduction.
