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Many biological and physiological processes depend upon directed migration of cells, which is typically mediated by chemical or physical gradients or by signal relay. Here we show that cells can be guided in a single preferred direction based solely on local asymmetries in nano/microtopography on subcellular scales. These asymmetries can be repeated, and thereby provide directional guidance, over arbitrarily large areas. The direction and strength of the guidance is sensitive to the details of the nano/microtopography, suggesting that this phenomenon plays a context-dependent role in vivo. We demonstrate that appropriate asymmetric nano/microtopography can unidirectionally bias internal actin polymerization waves and that cells move with the same preferred direction as these waves. This phenomenon is observed both for the pseudopod-dominated migration of the amoeboid Dictyostelium discoideum and for the lamellipod-driven migration of human neutrophils. The conservation of this mechanism across cell types and the asymmetric shape of many natural scaffolds suggest that actin-wave-based guidance is important in biology and physiology.

Contact formation of T cells with antigen presenting cells results in the engagement of T cell receptors (TCRs), recruitment and aggregation of signaling proteins into microclusters and ultimately, T cell activation. During this process, T cells undergo dramatic changes in cell shape and reorganization of the cytoskeleton. While the importance of the cytoskeleton in T cell activation is well known, the dynamics of the actin cytoskeleton and how it correlates with signaling clusters during the early stages of spreading is not well understood. Here, we used total internal reflection fluorescence microscopy to study the dynamics of actin reorganization during Jurkat T cell spreading and the role of integrin ligation by the adhesion molecule, vascular cell adhesion molecule (VCAM), in modulating actin dynamics. We found that when T cells spread on anti-CD3 antibody-coated glass surfaces, the cell edge exhibited repeated protrusions and retractions, which were driven by wave like patterns of actin that emerged from signaling microclusters. Addition of VCAM on the activating substrate altered the dynamics of actin both globally and locally, leading to a smooth expansion of the cell edge and the disappearance of waves. Our results suggest that the actin cytoskeleton in Jurkat cells is capable of organizing into spatial patterns initiated by TCR signaling and regulated by integrin signaling., (Copyright © 2013 Wiley Periodicals, Inc.)

Waves and dynamic patterns in chemical and physical systems have long interested experimentalists and theoreticians alike. Here we investigate a recent example within the context of cell biology, where waves of actin (a major component of the cytoskeleton) and its regulators (nucleation promoting factors, NPFs) are observed experimentally. We describe and analyze a minimal reaction diffusion model depicting the feedback between signalling proteins and filamentous actin (F-actin). Using numerical simulation, we show that this model displays a rich variety of patterning regimes. A relatively recent nonlinear stability method, the Local Perturbation Analysis (LPA), is used to map the parameter space of this model and explain the genesis of patterns in various linear and nonlinear patterning regimes. We compare our model for actin waves to others in the literature, and focus on transitions between static polarization, transient waves, periodic wave trains, and reflecting waves. We show, using LPA, that the spatially distributed model gives rise to dynamics that are absent in the kinetics alone. Finally, we show that the width and speed of the waves depend counter-intuitively on parameters such as rates of NPF activation, negative feedback, and the F-actin time scale., (© 2013 Published by Elsevier Ltd. All rights reserved.)

Emergence of dynamic patterns in the form of oscillations and waves on the cortex of single cells is a fascinating and enigmatic phenomenon. Herewe outline various theoretical frameworks used to model pattern formation with the goal of reducing complex, heterogeneous patterns into key parameters that are biologically tractable. We also review progress made in recent years on the quantitative and molecular definitions of these terms, which we believe have begun to transform single-cell dynamic patterns from a purely observational and descriptive subject to more mechanistic studies. Specifically, we focus on the nature of local excitable and oscillation events, their spatial couplings leading to propagatingwaves and the role of activemembrane. Instead of arguing for their functional importance,we prefer to consider such patterns as basic properties of dynamic systems.We discuss how knowledge of these patterns could be used to dissect the structure of cellular organization and how the network-centric view could help define cellular functions as transitions between different dynamical states. Last, we speculate on how these patterns could encode temporal and spatial information. This article is part of the theme issue 'Self-organization in cell biology'. [ABSTRACT FROM AUTHOR]

• Reviews experimental data of the biochemistry of phagocytosis. • Presents a mechanistic model of the actin waves in frustrated phagocytosis and compares it to previous models of actin waves. • Performs a steady state and bifurcation analysis of the resulting differential equations. • Using simulation of the resulting differential equations makes several predictions that are testable in the lab. Phagocytosis is a complex process by which phagocytes such as lymphocytes or macrophages engulf and destroy foreign bodies called pathogens in a tissue. The process is triggered by the detection of antibodies that trigger signaling mechanisms that control the changes of the cellular cytoskeleton needed for engulfment of the pathogen. A mathematical model of the entire process would be extremely complicated, because the signaling and cytoskeletal changes produce large mechanical deformations of the cell. Recent experiments have used a confinement technique that leads to a process called frustrated phagocytosis, in which the membrane does not deform, but rather, signaling triggers actin waves that propagate along the boundary of the cell. This eliminates the large-scale deformations and facilitates modeling of the wave dynamics. Herein we develop a model of the actin dynamics observed in frustrated phagocytosis and show that it can replicate the experimental observations. We identify the key components that control the actin waves and make a number of experimentally-testable predictions. In particular, we predict that diffusion coefficients of membrane-bound species must be larger behind the wavefront to replicate the internal structure of the waves. Our model is a first step toward a more complete model of phagocytosis, and provides insights into circular dorsal ruffles as well. [ABSTRACT FROM AUTHOR]