In addition, our model has a unique parameter (experiments

In addition, our model has a unique parameter (experiments. = 0.09 = 0.12 = 0.15 = 0.19 correspond to: = 2 (E), = 3 (F), = 4 (G), and = 5 (H).(EPS) pone.0201977.s010.eps (2.6M) GUID:?A754C9AD-7F60-4ECF-B61C-690D89A55FA0 S3 Fig: Variability in the motion pattern of a single cell. Example of a cell that switches from a slow moving state with only little net displacement to a state of rapid persistent motion.(EPS) pone.0201977.s011.eps (1.4M) GUID:?4DE9BC4F-9D7B-43E5-BF0E-A6FBBB87E6C3 Data Availability StatementAll relevant data are within the paper and its Supporting Information files. Abstract Amoeboid movement is one of the most widespread forms of cell motility that plays a key role in numerous biological contexts. While many aspects of this process are well investigated, the large cell-to-cell variability in the motile characteristics of an otherwise uniform population remains an open question that was largely ignored by previous models. In this article, we present a mathematical model of amoeboid motility that combines noisy bistable kinetics with a dynamic phase field for the cell shape. To capture cell-to-cell variability, we introduce a single parameter for tuning the balance between polarity formation and intracellular noise. We compare numerical simulations of our model to experiments with the social amoeba and a cells migrate spontaneously based on correlated deformations of their shape [8]. When exposed to a nonuniform chemoattractant profile, they bias their motion towards increasing chemoattractant concentrations. In this case, the variety of amoeboid cell shapes has also been attributed to strategies of accurate gradient sensing [9]. Prominent features of the cell shape dynamics are localized protrusions that are called pseudopods and can be considered the basic stepping units of amoeboid motion [10]. The ordered appearance of pseudopods and their biased formation in the presence of a chemoattractant gradient form the basis of persistent amoeboid motion [11, 12] and have inspired the use of random stepping models for mathematical descriptions of cell trajectories [13]. The resulting center-of-mass motion can be also EHNA hydrochloride described in terms of stochastic differential equations derived directly from the experimentally recorded trajectories [14C17]. These approaches were extended to biased EHNA hydrochloride random movement in a chemoattractant gradient [18] and highlight non-Brownian features of locomotion [19]. Depending on the nutrient conditions, may enter a developmental cycle that stronlgy affects cell speed and polarity. If food is abundant, cells remain in the vegetative state that is characterized by slow apolar motion, where pseudopods are formed in random directions. If food becomes sparse, a developmental cycle is initiated that ultimately leads to the formation of a multicellular fruiting structure. In the beginning, over the first hours of starvation-induced development, cells become chemotactic to cAMP, the speed increases, and cell movement becomes increasingly polar with pseudopods preferentially forming at a well-defined leading edge [20]. From experiments with fluorescently labeled constructs it is well known that under the influence of a chemoattractant gradient, a polar rearrangement of various intracellular signaling molecules and cytoskeletal components can be observed [21]. For example, the phospholipid PIP3 accumulates at the membrane in the front part of the cell, while at the sides and in the back predominantly PIP2 is found [22]. Consequently, also the PI3-kinase that phosphorylates PIP2 to PIP3 and the phosphatase PTEN that dephosphorylates PIP3 are polarly distributed along the cell membrane. Similarly, also the downstream cytoskeletal network exhibits a polar arrangement with freshly polymerized actin and the Arp2/3 complex at the leading edge, while the sides and EHNA hydrochloride back are enriched in myosin II. Also more complex patterns are observed, such as waves and oscillatory structures that emerge at different levels of the signaling system and the actin cytoskeleton [23C26]. Note that similar processes are also responsible for cell polarization and locomotion of neutrophils, which are highly motile white blood cells [27]. A variety of mathematical models have been proposed to rationalize the mechanisms of gradient sending, polarization, and locomotion of Ax-2 cells expressing a fluorescently labeled version of the Lifeact protein (C-terminally tagged with mRFP) as a marker for filamentous actin were grown in liquid Rabbit Polyclonal to P2RY11 culture flasks (HL5 media including glucose, Formedium, Hunstanton, UK) containing the required selection marker (G-418 sulfate: Cayman Chemical Company, USA, 10 defines the area of the cell and it is = 1 inside and = 0 outside the cell. The transition between these two values is smooth at the membrane which is defined by the value = 0.5. The evolution of the phase field follows the integro-differential equation.