No Arabic abstract
The aim of this paper is to develop suitable models for the phenomenon of cell blebbing, which allow for computational predictions of mechanical effects including the crucial interaction of the cell membrane and the actin cortex. For this sake we resort to a two phase-field model that uses diffuse descriptions of both the membrane and the cortex, which in particular allows for a suitable description of the interaction via linker protein densities. Besides the detailed modelling we discuss some energetic aspects of the models and present a numerical scheme, which allows to carry out several computational studies. In those we demonstrate that several effects found in experiments can be reproduced, in particular bleb formation by cortex rupture, which was not possible by previous models without the linker dynamics.
The phenomenological model for cell shape deformation and cell migration (Chen et.al. 2018; Vermolen and Gefen 2012) is extended with the incorporation of cell traction forces and the evolution of cell equilibrium shapes as a result of cell differentiation. Plastic deformations of the extracellular matrix are modelled using morphoelasticity theory. The resulting partial differential differential equations are solved by the use of the finite element method. The paper treats various biological scenarios that entail cell migration and cell shape evolution. The experimental observations in Mak et.al. (2013), where transmigration of cancer cells through narrow apertures is studied, are reproduced using a Monte Carlo framework.
In this paper, we propose and analyze a diffuse interface model for inductionless magnetohydrodynamic fluids. The model couples a convective Cahn-Hilliard equation for the evolution of the interface, the Navier-Stokes system for fluid flow and the possion quation for electrostatics. The model is derived from Onsagers variational principle and conservation laws systematically. We perform formally matched asymptotic expansions and develop several sharp interface models in the limit when the interfacial thickness tends to zero. It is shown that the sharp interface limit of the models are the standard incompressible inductionless magnetohydrodynamic equations coupled with several different interface conditions for different choice of the mobilities. Numerical results verify the convergence of the diffuse interface model with different mobilitiess.
Cells crawling through tissues migrate inside a complex fibrous environment called the extracellular matrix (ECM), which provides signals regulating motility. Here we investigate one such well-known pathway, involving mutually antagonistic signalling molecules (small GTPases Rac and Rho) that control the protrusion and contraction of the cell edges (lamellipodia). Invasive melanoma cells were observed migrating on surfaces with topography (array of posts), coated with adhesive molecules (fibronectin, FN) by Park et al., 2016. Several distinct qualitative behaviors they observed included persistent polarity, oscillation between the cell front and back, and random dynamics. To gain insight into the link between intracellular and ECM signaling, we compared experimental observations to a sequence of mathematical models encoding distinct hypotheses. The successful model required several critical factors. (1) Competition of lamellipodia for limited pools of GTPases. (2) Protrusion / contraction of lamellipodia influence ECM signaling. (3) ECM-mediated activation of Rho. A model combining these elements explains all three cellular behaviors and correctly predicts the results of experimental perturbations. This study yields new insight into how the dynamic interactions between intracellular signaling and the cells environment influence cell behavior.
The conventional cancer stem cell (CSC) theory indicates a hierarchy of CSCs and non-stem cancer cells (NSCCs), that is, CSCs can differentiate into NSCCs but not vice versa. However, an alternative paradigm of CSC theory with reversible cell plasticity among cancer cells has received much attention very recently. Here we present a generalized multi-phenotypic cancer model by integrating cell plasticity with the conventional hierarchical structure of cancer cells. We prove that under very weak assumption, the nonlinear dynamics of multi-phenotypic proportions in our model has only one stable steady state and no stable limit cycle. This result theoretically explains the phenotypic equilibrium phenomena reported in various cancer cell lines. Furthermore, according to the transient analysis of our model, it is found that cancer cell plasticity plays an essential role in maintaining the phenotypic diversity in cancer especially during the transient dynamics. Two biological examples with experimental data show that the phenotypic
Eukaryotic cell motility involves a complex network of interactions between biochemical components and mechanical processes. The cell employs this network to polarize and induce shape changes that give rise to membrane protrusions and retractions, ultimately leading to locomotion of the entire cell body. The combination of a nonlinear reaction-diffusion model of cell polarization, noisy bistable kinetics, and a dynamic phase field for the cell shape permits us to capture the key features of this complex system to investigate several motility scenarios, including amoeboid and fan-shaped forms as well as intermediate states with distinct displacement mechanisms. We compare the numerical simulations of our model to live cell imaging experiments of motile {it Dictyostelium discoideum} cells under different developmental conditions. The dominant parameters of the mathematical model that determine the different motility regimes are identified and discussed.