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Feeding fronts are a striking pattern of spatial distribution observed in both marine and terrestrial ecological systems. These fronts not only determine the abundance and distribution of prey populations, but on a broader scale they may also affect the structure and dynamics of entire communities. Several mechanisms leading to the formation of feeding fronts have been proposed, and chemotaxis has been suggested as an important component. Here we develop two mathematical models that show front formation can occur with simple kinesis (and without chemotaxis) in two marine invertebrates with different feeding habits: a microphagous sea star (Oreaster reticulatus) that feeds on sediments and an herbivorous sea urchin (Strongylocentrotus droebachiensis) that grazes kelp beds. We utilize a large body of detailed empirical information on movement pattern, foraging behavior, and front dynamics for each species to develop, parameterize, and evaluate our models. We found that our model predictions for the rate of advance of a front and its relationship to the density of consumers at the front were in close agreement with independently collected-, empirical observations in both systems. This work shows that simple local interactions between mobile consumers and a stationary resource can result in large-scale heterogeneous patterns of abundance of both species. Key words: aggregation; chemotaxis; ecological modeling; feeding fronts; kinesis; Oreaster reticulatus; sea star; sea urchin; spatial pattern; Strongylocentrotus droebachiensis.

Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II ceils, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic [Ca.sup.2+] and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through [Ca.sup.2+] activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury. lung inflammation; lung repair; chronic obstructive pulmonary disease

Blebbistatin is a myosin II-specific inhibitor. However, the mechanism and tissue specificity of the drug are not well understood. Blebbistatin blocked the chemotaxis of vascular smooth muscle cells (VSMCs) toward sphingosylphosphorylcholine (I[C.sub.50] = 26.1 [+ or -] 0.2 and 27.5 [+ or -] 0.5 [micro]M for GbaSM-4 and A7r5 cells, respectively) and platelet-derived growth factor BB (I[C.sub.50] = 32.3 [+ or -] 0.9 and 31.6 [+ or -] 1.3 [micro]M for GbaSM-4 and A7r5 cells, respectively) at similar concentrations. Immunofluorescence and fluorescent resonance energy transfer analysis indicated a blebbistatin-induced disruption of the actin-myosin interaction in VSMCs. Subsequent experiments indicated that blebbistatin inhibited the [Mg.sup.2+]-ATPase activity of the unphosphorylated (I[C.sub.50] = 12.6 [+ or -] 1.6 and 4.3 [+ or -] 0.5 [micro]M for gizzard and bovine stomach, respectively) and phosphorylated (I[C.sub.50] = 15.0 [+ or -] 0.6 [micro]M for gizzard) forms of purified smooth muscle myosin II, suggesting a direct effect on myosin II motor activity. It was further observed that the [Mg.sup.2+]-ATPase activities of gizzard myosin II fragments, heavy meromyosin (I[C.sub.50] = 14.4 [+ or -] 1.6 [micro]M) and subfragment 1 (I[C.sub.50] = 5.5 [+ or -] 0.4 [micro]M), were also inhibited by blebbistatin. Assay by in vitro motility indicated that the inhibitory effect of blebbistatin was reversible. Electron-microscopic evaluation showed that blebbistatin induced a distinct conformational change (i.e., swelling) of the myosin II head. The results suggest that the site of blebbistatin action is within the S1 portion of smooth muscle myosin II. Boyden chamber; fluorescence resonance energy transfer; ATPase; in vitro motility assay; electron microscopy

Chemotaxis is the ability of cells to move in the direction of an external gradient of signaling molecules. Cells are guided by actin-filled protrusions in the front, whereas myosin filaments retract the rear of the cell. Previous work demonstrated that chemotaxis of unpolarized amoeboid Dictyostelium discoideum cells is mediated by two parallel pathways, phosphoinositide-3-kinase (PI3K) and phospholipase A2 (PLA2). Here, we show that polarized cells exhibit very good chemotaxis with inhibited PI3K and PLA2 activity. Using genetic screens, we demonstrate that this activity is mediated by a soluble guanylyl cyclase, providing two signals. The protein localizes to the leading edge where it interacts with actin filaments, whereas the cyclic guanosine monophosphate product induces myosin filaments in the rear of the cell. We conclude that chemotaxis is mediated by multiple signaling pathways regulating protrusions at the front and rear of the cell. Cells that express only rear activity are polarized but do not exhibit chemotaxis, whereas cells with only front signaling are unpolarized but undergo chemotaxis.

Wiring up the nervous system depends on the precise guidance of axonal growth cones to their targets. A key mechanism underlying this guidance is chemotaxis, whereby growth cones detect and follow molecular gradients. Although recent work has uncovered many of the molecules involved in this process, the mechanisms underlying chemotactic axon guidance are still unclear. Here we compare growth cones with neutrophils and Dictyostelium discoideum, systems for which a clear conceptual framework for chemotaxis has recently emerged. This analogy suggests particular ways in which the three key steps of directional sensing, polarisation and motility might be implemented in chemotaxing growth cones.

Polarization of chemotaxing cells depends on positive feedback loops that amplify shallow gradients of chemoattractants into sharp intracellular responses. In particular, reciprocal activation of phosphatidylinositol 3-kinases (PI3Ks) and small GTPases like Rac leads to accumulation, at the leading edge, of the PI3K product phosphatidylinositol 3,4,5-trisphosphate (PIP3). Mice carrying a 'knockin' allele of the G protein-coupled receptor (GPCR)-activated PI3K [gamma] encoding a plasma membrane-targeted protein appeared normal, but their leukocytes showed GPCR-uncoupled PIP3 accumulation. In vivo, the mutation increased proliferation and decreased apoptosis, leading to leukocytosis and delayed resolution of inflammation in wound healing. Mutant leukocytes showed significantly impaired directional cell migration in response to chemoattractants. Stimulated mutant macrophages did not polarize PIP3 and showed a shortened Rac activation because of enhanced PI3K-dependent activation of RacGAPs. Together with the finding that chemoattractants stimulate a PIP3-dependent GAP activation in wild-type macrophages, these results identify a molecular mechanism involving PI3K- and RacGAP-dependent negative control of Rac that limits and fine-tunes feedback loops promoting cell polarization and directional motility. chemotaxis | signal transduction | inflammation

We have analyzed chemotaxis of neutrophil-differentiated HL60 cells in microfluidic devices that create exponential gradients of the chemoattractant, f-Met-Leu-Phe (fMLP). Such gradients expose each cell to a difference in fMLP concentration ([DELTA]C) across its diameter that is directly proportional to the ambient concentration (C) at that cell's position in the gradient, so the ratio [DELTA]C/C is constant everywhere. Cells exposed to ambient fMLP concentrations near the constant of dissociation ([K.sub.d]) for fMLP binding to its receptor ([approximately equal to]10 nM) crawl much less frequently when [DELTA]C/C is 0.05 than when it is 0.09 or 0.13. Hence, cells can detect the gradient across their diameter without moving and, thus, without experiencing temporal changes in attractant concentration. At all [DELTA]C/C ratios tested, the average chemotactic prowess of individual cells (indicated by the distance a cell traveled in the correct direction divided by the length of its migration path) is maximal for cells that start migrating at concentrations near the Kd and progressively decreases at higher or lower starting concentrations. chemoattractant | gradient | neutrophils

Cell motility plays an essential role in many biological systems, but precise quantitative knowledge of the biophysical processes involved in cell migration is limited. Better measurements are needed to ultimately build models with predictive capabilities. We present an improved force cytometry method and apply it to the analysis of the dynamics of the chemotactic migration of the amoeboid form of Dictyostelium discoideum. Our explicit calculation of the force field takes into account the finite thickness of the elastic substrate and improves the accuracy and resolution compared with previous methods. This approach enables us to quantitatively study the differences in the mechanics of the migration of wildtype (WT) and mutant cell lines. The time evolution of the strain energy exerted by the migrating ceils on their substrate is quasi-periodic and can be used as a simple indicator of the stages of the cell motility cycle. We have found that the mean velocity of migration v and the period of the strain energy T cycle are related through a hyperbolic law v = L/T, where L is a constant step length that remains unchanged in mutants with adhesion or contraction defects. Furthermore, when cells adhere to the substrate, they exert opposing pole forces that are orders of magnitude higher than required to overcome the resistance from their environment. Dictyostelium | myosin | traction forces | cytoskeleton | chemotaxis

We develop a theoretical description of sperm chemotaxis. Sperm cells of many species are guided to the egg by chemoattractants, a process called chemotaxis. Motor proteins in the flagellum of the sperm generate a regular beat of the flagellum, which propels the sperm in a fluid. In the absence of a chemoattractant, sperm swim in circles in two dimensions and along helical paths in three dimensions. Chemoattractants stimulate a signaling system in the flagellum, which regulates the motors to control sperm swimming. Our theoretical description of sperm chemotaxis in two and three dimensions is based on a generic signaling module that regulates the curvature and torsion of the swimming path. In the presence of a chemoattractant, swimming paths are drifting circles in two dimensions and deformed helices in three dimensions. The swimming paths can be described by a dynamical system that exhibits different dynamic regimes, which correspond to different chemotactic behaviours. We conclude that sampling a concentration field of chemoattractant along circular and helical swimming paths is a robust strategy for chemotaxis that works reliably for a vast range of parameters. helicalklinotaxis | sperm swimming flagellarpropulsion signaling systems | adaptation

Mast cells are long-lived cells that are principally recognized for their effector function in helminth infections and allergic reactions. These cells are derived from pluripotential hematopoietic stem cells in the bone marrow that give rise to committed mast cell progenitors in the blood and are recruited to tissues, where they mature. Little is known about the chemotactic signals responsible for recruitment of progenitors and localization of mature mast cells. A mouse model was set up to identify possible mast cell progenitor chemoattractants produced during repeated allergen challenge in vivo. After the final challenge, the nasal mucosa was removed to produce conditioned medium, which was tested in chemotaxis assays against 2-wk murine bone marrow-derived [c-kit.sup.+] mast cells (BMMC). A single peak of chemotactic activity was seen on reverse-phase HPLC with a retention time and electrospray mass spectrum consistent with prostaglandin [E.sub.2] (PG[E.sub.2]). This lipid was found to be a highly potent chemoattractant for immature (2-wk) and also mature (10-wk) BMMC in vitro. Fluorescently labeled 2-wk [c-kit.sup.+] BMMC, when injected intravenously, accumulated in response to intradermally injected PG[E.sub.2]. Analysis using TaqMan showed mRNA expression of the PGE2 receptors 3 (EP3) and 4 (EP4) on 2- and 10-wk BMMC. Chemotaxis induced by PG[E.sub.2] was mimicked by EP3 agonists, blocked by an EP3 receptor antagonist, and partially inhibited by a MAPKK inhibitor. These results show an unexpected function for PG[E.sub.2] in the chemotaxis of mast cells. allergy | eicosanoids | migration