Browsing by Author "Rappel, Wouter-Jan"
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Item Alignment of cellular motility forces with tissue flow as a mechanism for efficient wound healing(National Academy of Science, 2012) Basan, Markus; Elgeti, Jens; Hannezo, Edouard; Rappel, Wouter-Jan; Levine, Herbert; Center for Theoretical Biological PhysicsRecent experiments have shown that spreading epithelial sheets exhibit a long-range coordination of motility forces that leads to a buildup of tension in the tissue, which may enhance cell division and the speed of wound healing. Furthermore, the edges of these epithelial sheets commonly show finger-like protrusions whereas the bulk often displays spontaneous swirls of motile cells. To explain these experimental observations, we propose a simple flocking-type mechanism, in which cells tend to align their motility forceswith their velocity. Implementing this idea in amechanical tissue simulation, the proposed model gives rise to efficient spreading and can explain the experimentally observed long-range alignment of motility forces in highly disordered patterns, as well as the buildup of tensile stress throughout the tissue. Our model also qualitatively reproduces the dependence of swirl size and swirl velocity on cell density reported in experiments and exhibits an undulation instability at the edge of the spreading tissue commonly observed in vivo. Finally, we study the dependence of colony spreading speed on important physical and biological parameters and derive simple scaling relations that show that coordination of motility forces leads to an improvement of the wound healing process for realistic tissue parameters.Item Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance(Public Library of Science, 2016) Camley, Brian A.; Zimmermann, Juliane; Levine, Herbert; Rappel, Wouter-Jan; Center for Theoretical Biological PhysicsSingle eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of “collective guidance” computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster’s size—clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signals; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and strong short range adhesion. If cell-cell adhesion is absent, and the cluster cohesion is instead provided by a co-attraction mechanism, e.g. chemotaxis toward a secreted molecule, collective guidance may still function. However, new behaviors, such as cluster rotation, may also appear in this case. Co-attraction and adaptation allow for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion.Item Excitable waves and direction-sensing inᅠDictyostelium discoideum: steps towards a chemotaxis model(IOP Publishing Ltd, 2016) Bhowmik, Arpan; Rappel, Wouter-Jan; Levine, Herbert; Center for Theoretical Biological PhysicsIn recent years, there have been significant advances in our understanding of the mechanisms underlying chemically directed motility by eukaryotic cells such as Dictyostelium. In particular, the local excitation and global inhibition (LEGI) model has proven capable of providing a framework for quantitatively explaining many experiments that present Dictyostelium cells with tailored chemical stimuli and monitor their subsequent polarization. In their natural setting, cells generate their own directional signals via the detection and secretion of cyclic adenosine monophosphate (cAMP). Here, we couple the LEGI approach to an excitable medium model of the cAMP wave-field that is propagated by the cells and investigate the possibility for this class of models to enable accurate chemotaxis to the cAMP waveforms expected in vivo. Our results indicate that the ultra-sensitive version of the model does an excellent job in providing natural wave rectification, thereby providing a compelling solution to the 'back-of-the-wave paradox' during cellular aggregation.Item How input fluctuations reshape the dynamics of a biological switching system(2012) Hu, Bo; Kessler, David A.; Rappel, Wouter-Jan; Levine, Herbert; National Science Foundation; Center for Theoretical Biological Physics; American Physical SocietyAn important task in quantitative biology is to understand the role of stochasticity in biochemical regulation. Here, as an extension of our recent work [Phys. Rev. Lett. 107, 148101 (2011)], we study how input fluctuations affect the stochastic dynamics of a simple biological switch. In our model, the on transition rate of the switch is directly regulated by a noisy input signal, which is described as a non-negative mean-reverting diffusion process. This continuous process can be a good approximation of the discrete birth-death process and is much more analytically tractable.Within this setup, we apply the Feynman-Kac theorem to investigate the statistical features of the output switching dynamics. Consistent with our previous findings, the input noise is found to effectively suppress the input-dependent transitions.We show analytically that this effect becomes significant when the input signal fluctuates greatly in amplitude and reverts slowly to its mean.Item How input noise limits biochemical sensing in ultrasensitive systems(American Physical Society, 2014) Hu, Bo; Rappel, Wouter-Jan; Levine, Herbert; Center for Theoretical Biological PhysicsMany biological processes are regulated by molecular devices that respond in an ultrasensitive fashion to upstream signals. An important question is whether such ultrasensitivity improves or limits its ability to read out the (noisy) input stimuli. Here, we develop a simple model to study the statistical properties of ultrasensitive signaling systems. We demonstrate that the output sensory noise is always bounded, in contrast to earlier theories using the small noise approximation, which tends to overestimate the impact of noise in ultrasensitive pathways. Our analysis also shows that the apparent sensitivity of the system is ultimately constrained by the input signal-to-noise ratio. Thus, ultrasensitivity can improve the precision of biochemical sensing only to a finite extent. This corresponds to a new limit for ultrasensitive signaling systems, which is strictly tighter than the Berg-Purcell limit.Item Intercellular Stress Reconstitution from Traction Force Data(Elsevier, 2014) Zimmermann, Juliane; Hayes, Ryan L.; Basan, Markus; Onuchic, José N.; Rappel, Wouter-Jan; Levine, Herbert; Center for Theoretical Biological PhysicsCells migrate collectively during development, wound healing, and cancer metastasis. Recently, a method has been developed to recover intercellular stress in monolayers from measured traction forces upon the substrate. To calculate stress maps in two dimensions, the cell sheet was assumed to behave like an elastic material, and it remains unclear to what extent this assumption is valid. In this study, we simulate our recently developed model for collective cell migration, and compute intercellular stress maps using the method employed in the experiments. We also compute these maps using a method that does not depend on the traction forces or material properties. The two independently obtained stress patterns agree well for the parameters we have probed and provide a verification of the validity of the experimental method.Item Periodic Migration in a Physical Model of Cells on Micropatterns(American Physical Society, 2013) Camley, Brian A.; Zhao, Yanxiang; Li, Bo; Levine, Herbert; Rappel, Wouter-Jan; Center for Theoretical Biological PhysicsWe extend a model for the morphology and dynamics of a crawling eukaryotic cell to describe cells on micropatterned substrates. This model couples cell morphology, adhesion, and cytoskeletal flow in response to active stresses induced by actin and myosin. We propose that protrusive stresses are only generated where the cell adheres, leading to the cellメs effective confinement to the pattern. Consistent with experimental results, simulated cells exhibit a broad range of behaviors, including steady motion, turning, bipedal motion, and periodic migration, in which the cell crawls persistently in one direction before reversing periodically. We show that periodic motion emerges naturally from the coupling of cell polarization to cell shape by reducing the model to a simplified one-dimensional form that can be understood analytically.Item The physics of eukaryotic chemotaxis(AIP Publishing LLC, 2013) Levine, Herbert; Rappel, Wouter-JanA small scratch on the skin can be quite painful. Fortunately, the pain is transitory and dissipates quickly once the wound heals. The healing process is facilitated by neutrophils, a type of white blood cell that removes bacteria and other foreign materials from a wound. Neutrophils normally reside in your circulatory system but, when needed, are able to leave the bloodstream and efficiently navigate through connective tissue to the injured area. How do they figure out where to go? The answer is chemotaxis, the process of cells following chemical gradients. In addition to wound healing, chemotaxis is important to many other biological processes. Chemical information can help sperm find the egg cell during fertilization. In embryonic development, cells are often directed to their proper location through gradients. Chemotaxis can also aid the spread of cancer during metastasis, the process by which cells leave the primary tumor and seed new tumors in other parts of the body. Experiments have shown that gradients of growth factors guide an initial step in the metastatic process; that step involves the movement of malignant cells away from the tumor and toward blood vessels.