Collective signal processing in cluster chemotaxis: roles of adaptation, amplification, and co-attraction in collective guidance

Single 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 signal; 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 to function. 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. Together, the combination of co-attraction and adaptation allows for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion.Comment: This article extends some results previously presented in arXiv:1506.0669

Emergent collective chemotaxis without single-cell gradient sensing

Many eukaryotic cells chemotax, sensing and following chemical gradients. However, experiments have shown that even under conditions when single cells cannot chemotax, small clusters may still follow a gradient. This behavior has been observed in neural crest cells, in lymphocytes, and during border cell migration in Drosophila, but its origin remains puzzling. Here, we propose a new mechanism underlying this "collective guidance", and study a model based on this mechanism both analytically and computationally. Our approach posits that the contact inhibition of locomotion (CIL), where cells polarize away from cell-cell contact, is regulated by the chemoattractant. Individual cells must measure the mean attractant value, but need not measure its gradient, to give rise to directional motility for a cell cluster. We present analytic formulas for how cluster velocity and chemotactic index depend on the number and organization of cells in the cluster. The presence of strong orientation effects provides a simple test for our theory of collective guidance.Comment: Updated with additional simulations. Aspects of v1 of this paper about adaptation and amplification have been extended and turned into a separate paper, and removed from the current versio

Periodic migration in a physical model of cells on micropatterns

We 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'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.Comment: 15 pages (includes supplementary material as an appendix). Recently accepted to Physical Review Letter

Episodic and Semantic Autobiographical Memory and Everyday Memory during Late Childhood and Early Adolescence

Few studies have examined both episodic and semantic autobiographical memory (AM) performance during late childhood and early adolescence. Using the newly developed Children’s Autobiographical Interview (CAI), the present study examined the effects of age and sex on episodic and semantic AM and everyday memory in 182 children and adolescents. Results indicated that episodic and semantic AM both improved between 8 and 16 years of age; however, age-related changes were larger for episodic AM than for semantic AM. In addition, females were found to recall more episodic AM details, but not more semantic AM details, than males. Importantly, this sex difference in episodic AM recall was attenuated under conditions of high retrieval support (i.e., the use of probing questions). The ability to clearly visualize past events at the time of recollection was related to children’s episodic AM recall performance, particularly the retrieval of perceptual details. Finally, similar age and sex effects were found between episodic AM and everyday memory ability (e.g., memory for everyday activities). More specifically, older participants and females exhibited better episodic AM and everyday memory performance than younger participants and males. Overall, the present study provides important new insight into both episodic and semantic AM performance, as well as the relation between episodic AM and everyday memory, during late childhood and adolescence

Analysis of a Convective Reaction-Diffusion Equation II

We study the large time behavior of positive solutions of the semilinear parabolic equation $u_t = u_{xx} + \varepsilon (g(u))_x + f(u)$, $0 \u3c x \u3c L$, $\varepsilon \in {\bf R}$, subject to $u(0,t) = u(L,t) = 0$. The model problem in which the results apply is $g(u) = u^m$ and $f(u) = u^p 1 \leqq m \u3c p$. The steady state problem is analyzed in some detail, and results about finite time blow up are proved

Addressing the Fertility Needs of HIV-Seropositive Males

An increasing number of serodiscordant couples are utilizing advanced reproductive technologies to address their reproductive needs. Recent literature has demonstrated that it is not only technically possible but also safe to utilize sperm-washing techniques to allow for the creation of embryos, thereby preventing both horizontal and vertical transmission of HIV. This article addresses the strengths and weakness of various reproductive techniques and discusses our experience at Columbia University (NY, USA), the location of the largest HIV-focused fertility program in the USA

Monitoring the introduction of pneumococcal conjugate vaccines into West Africa: design and implementation of a population-based surveillance system.

Routine use of pneumococcal conjugate vaccines (PCVs) in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes. We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD. Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government. This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings

Translational Research and Medicine at NASA: From Earth to Space and Back Again

The Space Environment provides many challenges to the human physiology and therefore to extended habitation and exploration. Translational research and medical strategies are meeting these challenges by combining Earth based medical solutions with innovative and developmental engineering approaches. Translational methodologies are current applied to spaceflight related dysregulations in the areas of: (1) cardiovascular fluid shifts, intracranial hypertension and neuro-ocular impairment 2) immune insufficiency and suppression/viral re-expression, 3) bone loss and fragility (osteopenia/osteoporosis) and muscle wasting, and finally 4) radiation sensitivity and advanced ageing. Over 40 years of research into these areas have met with limited success due to lack of tools and basic understanding of central issues that cause physiologic maladaptaion and distrupt homeostatis. I will discuss the effects of living in space (reduced gravity, increased radiation and varying atmospheric conditions [EVA]) during long-duration, exploration-class missions and how translational research has benefited not only space exploration but also Earth based medicine. Modern tools such as telemedicine advances in genomics, proteomics, and metabolomics (Omicssciences) has helped address syndromes, at the systemic level by enlisting a global approach to assessing spaceflight physiology and to develop countermeasures thereby permitting our experience in space to be translated to the Earth's medical community