Spontaneous transitions between amoeboid and keratocyte-like modes of migration

The motility of adherent eukaryotic cells is driven by the dynamics of the actin cytoskeleton. Despite the common force-generating actin machinery, different cell types often show diverse modes of locomotion that differ in their shape dynamics, speed, and persistence of motion. Recently, experiments in Dictyostelium discoideum have revealed that different motility modes can be induced in this model organism, depending on genetic modifications, developmental conditions, and synthetic changes of intracellular signaling. Here, we report experimental evidence that in a mutated D. discoideum cell line with increased Ras activity, switches between two distinct migratory modes, the amoeboid and fan-shaped type of locomotion, can even spontaneously occur within the same cell. We observed and characterized repeated and reversible switchings between the two modes of locomotion, suggesting that they are distinct behavioral traits that coexist within the same cell. We adapted an established phenomenological motility model that combines a reaction-diffusion system for the intracellular dynamics with a dynamic phase field to account for our experimental findings.Comment: Some references pointing at figures in the supplement and therefore are not correctly displayed. The supplement is available at zenodo.or

The unicellular microorganisms "Amoeba Proteus" locomotion simulation with the use of movable cellular automata method

Работа посвящена моделированию амебоидной подвижности. В качестве объекта выбран одноклеточный микроорганизм «Amoeba Proteus», рассмотрены основные принципы локомоции, на основании которых построена модель. В качестве метода моделирования задействован аппарат подвижных клеточных автоматов. Получена компьютерная модель, имитирующая амебоидную локомоцию

From Molecular Signal Activation to Locomotion: An Integrated, Multiscale Analysis of Cell Motility on Defined Matrices

The adhesion, mechanics, and motility of eukaryotic cells are highly sensitive to the ligand density and stiffness of the extracellular matrix (ECM). This relationship bears profound implications for stem cell engineering, tumor invasion and metastasis. Yet, our quantitative understanding of how ECM biophysical properties, mechanotransductive signals, and assembly of contractile and adhesive structures collude to control these cell behaviors remains extremely limited. Here we present a novel multiscale model of cell migration on ECMs of defined biophysical properties that integrates local activation of biochemical signals with adhesion and force generation at the cell-ECM interface. We capture the mechanosensitivity of individual cellular components by dynamically coupling ECM properties to the activation of Rho and Rac GTPases in specific portions of the cell with actomyosin contractility, cell-ECM adhesion bond formation and rupture, and process extension and retraction. We show that our framework is capable of recreating key experimentally-observed features of the relationship between cell migration and ECM biophysical properties. In particular, our model predicts for the first time recently reported transitions from filopodial to “stick-slip” to gliding motility on ECMs of increasing stiffness, previously observed dependences of migration speed on ECM stiffness and ligand density, and high-resolution measurements of mechanosensitive protrusion dynamics during cell motility we newly obtained for this study. It also relates the biphasic dependence of cell migration speed on ECM stiffness to the tendency of the cell to polarize. By enabling the investigation of experimentally-inaccessible microscale relationships between mechanotransductive signaling, adhesion, and motility, our model offers new insight into how these factors interact with one another to produce complex migration patterns across a variety of ECM conditions

Modeling cell crawling strategies with a bistable model: From amoeboid to fan-shaped cell motion

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

Role of modulators of small GTPases in chemotaxis, cytokinesis and development in Dictyostelium Discoideum

The work described here shows the complexity of GTPase signalling in an apparently simple organism Dictyostelium discoideum. Ras Guanine nucleotide exchange factor RasGEF Q is one out of at least 25 RasGEFs in D. discoideum. Here we show that it specifically regulates myosin II functions by regulating myosin phosphorylation. RasGEF Q activates the Ras isoform RasB upon stimulation with cAMP. Activated RasB can directly or indirectly activate Myosin Heavy chain kinase A (MHCK A) which then phosphorylates the myosin II heavy chain. Phosphorylated myosin II cannot assemble into filaments and is thus a non-functional form. Furthermore, a DEP domain in RasGEF Q appears to be critical for activating RasGEF Q by release from an autoinhibited state. Studies on the multidomain Rac Guanine nucleotide exchange factor GxcDD show that it is required for the early phases of development in chemotactic migration and streaming behaviour. The characterization of its single domains revealed that the CH domain (Calponin homology domain) of GxcDD functions as a membrane association domain, the RhoGEF domain can physically interact with a subset of Rac GTPases and the ArfGAP-PH tandem accumulates in cortical regions of the cell and in phagosomes. Our results also suggest that a conformational change is required for activation of GxcDD, which would be important for its downstream signaling. Studies on the IQGAP related protein GAPA showed that it associates with two actin-corsslinking protein, namely Filamin and Cortexillin I. GAPA is required for cytokinesis and localizes to the cleavage furrow during cytokinesis in a cortexillin I dependent way. We also observed that GAPA is required for proper phototaxis as is its binding partner Filamin