Cell Mechanics and Adhesion: Cell Blebbing and Malaria Parasite Invasion

Cell mechanics and adhesion play an important role in biological systems. We focus on two examples in this thesis, stress-induced cell blebbing and red blood cell deformation during the invasion by malaria parasites. To investigate both processes, simulation models are employed and their dependence on various parameters, such as membrane properties or adhesion kinetics, are studied. A coarse-grained cell model, which includes a lipid-bilayer cell membrane and a bulk cytoskeleton, is introduced. To incorporate effects of fluid environment, we additionally present two simulation frameworks, Brownian dynamics and dissipative particle dynamics. Both methods allow for an effective formulation of fluid properties, such as viscosity and thermal fluctuations. The elastic response of the cell is studied by microplates compression and the effect of various simulation parameters on cell deformation is analyzed, e.g. the bulk Young's modulus and the stretching resistance of the cell membrane. It is shown that the total elastic response can be described by a superposition of the elastic parameters of the cytoskeleton and cell membrane. Cell blebbing is connected to a number of cell processes such as cell death and cell motility. A membrane bleb is a protrusion formed by a cell membrane that locally detaches from an underlying cell structure such as a cytoskeleton. Stress-induced cell blebbing is studied by adding a contraction mechanism to the employed bulk cytoskeleton model. Additionally, a dynamic, bond-based adhesion between cell membrane and inner network is introduced. The model is able to reproduce cell blebbing, which occurs for a limited parameter range. By employing mean-field calculations and computer simulations, the effects of cell membrane properties and the adhesion on cell blebbing are separated. A number of scaling laws for the onset of blebbing are derived by quantifying the effects of various simulation parameters, e.g. the membrane bending rigidity and the number of adhesion binding sites. Today, malaria is still one of the deadliest diseases and attributes to about half a million human deaths every year. Malaria parasites reproduce by invading red blood cells in the human blood stream. Before the invasion takes place, a parasite may induce various deformations at the membrane of a targeted red blood cell. According to the passive compliance hypothesis, these deformations are a result of the adhesion of the parasite to the cell membrane and aid the malaria parasite alignment. The successful alignment of the parasite head is an important step in the invasion process. To test these assumptions, simulations of a red blood cell and a parasite are employed, in which they interact either via an attractive potential or through a bond-based, dynamic adhesion. Both employed interaction models can reproduce red blood cell deformations comparable to those in experiments. The deformations are induced by the mechanical interaction between parasite and red blood cell. The adhesion force required for these deformations is on the same order of magnitude as measured in experiments. With the bond-based adhesion, the parasite dynamics and red blood cell deformations observed in vitro are reproduced. Parasite alignment is quantified by a number of parameters, such as alignment angle and alignment time, and a reliable parasite alignment through the bond-based adhesion is shown. The effect of various simulation properties on parasite alignment is studied and the egg-like parasite shape, which was measured in in vitro and in vivo experiments, is shown to lead to the highest alignment probability. Other important aspects for the parasite alignment are the average bond lifetimes and the length of bonds. Finally, the importance of the red blood cell deformations for a successful parasite is shown and it is concluded that the passive compliance hypothesis can explain a number of experimental observations of malaria parasite alignment.