Dynamics of a deformable self-propelled particle under external forcing

We investigate dynamics of a self-propelled deformable particle under external field in two dimensions based on the model equations for the center of mass and a tensor variable characterizing deformations. We consider two kinds of external force. One is a gravitational-like force which enters additively in the time-evolution equation for the center of mass. The other is an electric-like force supposing that a dipole moment is induced in the particle. This force is added to the equation for the deformation tensor. It is shown that a rich variety of dynamics appears by changing the strength of the forces and the migration velocity of self-propelled particle

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

Cytoskeletal dynamics during cell behaviours ranging from endocytosis and exocytosis to cell division and movement is controlled by a complex network of signalling pathways, the full details of which are as yet unresolved. Here we show that SILAC-based proteomic methods can be used to characterize the rapid chemoattractant-induced dynamic changes in the actin–myosin cytoskeleton and regulatory elements on a proteome-wide scale with a second to minute timescale resolution. This approach provides novel insights in the ensemble kinetics of key cytoskeletal constituents and association of known and novel identified binding proteins. We validate the proteomic data by detailed microscopy-based analysis of in vivo translocation dynamics for key signalling factors. This rapid large-scale proteomic approach may be applied to other situations where highly dynamic changes in complex cellular compartments are expected to play a key role

A Stochastic Description of Dictyostelium Chemotaxis

Chemotaxis, the directed motion of a cell toward a chemical source, plays a key role in many essential biological processes. Here, we derive a statistical model that quantitatively describes the chemotactic motion of eukaryotic cells in a chemical gradient. Our model is based on observations of the chemotactic motion of the social ameba Dictyostelium discoideum, a model organism for eukaryotic chemotaxis. A large number of cell trajectories in stationary, linear chemoattractant gradients is measured, using microfluidic tools in combination with automated cell tracking. We describe the directional motion as the interplay between deterministic and stochastic contributions based on a Langevin equation. The functional form of this equation is directly extracted from experimental data by angle-resolved conditional averages. It contains quadratic deterministic damping and multiplicative noise. In the presence of an external gradient, the deterministic part shows a clear angular dependence that takes the form of a force pointing in gradient direction. With increasing gradient steepness, this force passes through a maximum that coincides with maxima in both speed and directionality of the cells. The stochastic part, on the other hand, does not depend on the orientation of the directional cue and remains independent of the gradient magnitude. Numerical simulations of our probabilistic model yield quantitative agreement with the experimental distribution functions. Thus our model captures well the dynamics of chemotactic cells and can serve to quantify differences and similarities of different chemotactic eukaryotes. Finally, on the basis of our model, we can characterize the heterogeneity within a population of chemotactic cells

Environmental enrichment has no effect on the development of dopaminergic and GABAergic fibers during methylphenidate treatment of early traumatized gerbils

It is widely believed, that environmental factors play a crucial role in the etiology and outcome of psychiatric diseases such as Attention-Deficit/Hyperactivity Disorder (ADHD). A former study from our laboratory has shown that both methylphenidate (MP) and handling have a positive effect on the dopaminergic fiber density in the prefrontal cortex (PFC) of early traumatized gerbils (Meriones unguiculatus). The current study was performed to investigate if enriched environment during MP application has an additional influence on the dopaminergic and GABAergic fiber densities in the PFC and amygdala in this animal model

TOR kinase complexes and cell migration

Cell migration is a fundamental process in a wide array of biological and pathological responses. It is regulated by complex signal transduction pathways in response to external cues that couple to growth factor and chemokine receptors. In recent years, the target of rapamycin (TOR) kinase, as part of either TOR complex 1 (TORC1) or TOR complex 2 (TORC2), has been shown to be an important signaling component linking external signals to the cytoskeletal machinery in a variety of cell types and organisms. Thus, these complexes have emerged as key regulators of cell migration and chemotaxis

Subcellular optogenetic inhibition of G proteins generates signaling gradients and cell migration

Cells sense gradients of extracellular cues and generate polarized responses such as cell migration and neurite initiation. There is static information on the intracellular signaling molecules involved in these responses, but how they dynamically orchestrate polarized cell behaviors is not well understood. A limitation has been the lack of methods to exert spatial and temporal control over specific signaling molecules inside a living cell. Here we introduce optogenetic tools that act downstream of native G protein–coupled receptor (GPCRs) and provide direct control over the activity of endogenous heterotrimeric G protein subunits. Light-triggered recruitment of a truncated regulator of G protein signaling (RGS) protein or a Gβγ-sequestering domain to a selected region on the plasma membrane results in localized inhibition of G protein signaling. In immune cells exposed to spatially uniform chemoattractants, these optogenetic tools allow us to create reversible gradients of signaling activity. Migratory responses generated by this approach show that a gradient of active G protein αi and βγ subunits is sufficient to generate directed cell migration. They also provide the most direct evidence so for a global inhibition pathway triggered by Gi signaling in directional sensing and adaptation. These optogenetic tools can be applied to interrogate the mechanistic basis of other GPCR-modulated cellular functions

Gene Expression Profiles of the NCI-60 Human Tumor Cell Lines Define Molecular Interaction Networks Governing Cell Migration Processes

Although there is extensive information on gene expression and molecular interactions in various cell types, integrating those data in a functionally coherent manner remains challenging. This study explores the premise that genes whose expression at the mRNA level is correlated over diverse cell lines are likely to function together in a network of molecular interactions. We previously derived expression-correlated gene clusters from the database of the NCI-60 human tumor cell lines and associated each cluster with function categories of the Gene Ontology (GO) database. From a cluster rich in genes associated with GO categories related to cell migration, we extracted 15 genes that were highly cross-correlated; prominent among them were RRAS, AXL, ADAM9, FN14, and integrin-beta1. We then used those 15 genes as bait to identify other correlated genes in the NCI-60 database. A survey of current literature disclosed, not only that many of the expression-correlated genes engaged in molecular interactions related to migration, invasion, and metastasis, but that highly cross-correlated subsets of those genes engaged in specific cell migration processes. We assembled this information in molecular interaction maps (MIMs) that depict networks governing 3 cell migration processes: degradation of extracellular matrix, production of transient focal complexes at the leading edge of the cell, and retraction of the rear part of the cell. Also depicted are interactions controlling the release and effects of calcium ions, which may regulate migration in a spaciotemporal manner in the cell. The MIMs and associated text comprise a detailed and integrated summary of what is currently known or surmised about the role of the expression cross-correlated genes in molecular networks governing those processes

Effects of enriched and of restricted rearing on both neurogenesis and synaptogenesis in the hippocampal dentate gyrus of adult gerbils (Meriones unguiculatus).

Keller A, Bagorda F, Hildebrandt K, Teuchert-Noodt G. Effects of enriched and of restricted rearing on both neurogenesis and synaptogenesis in the hippocampal dentate gyrus of adult gerbils (Meriones unguiculatus). NEUROLOGY PSYCHIATRY AND BRAIN RESEARCH. 2000;8(3):101-107.Current investigations on hippocampal neurogenesis and plasticity are usually performed with animals from standard laboratory rearing and housing. Yet, it is still unclear whether standard rearing conditions may destabilize those individual brain transmitters during peri- and postnatal development which control neurogenesis for life. The objective of the present study was to quantify cell proliferation rates and synaptic remodeling in the dentate gyrus of: male gerbils reared and housed either grouped under enriched (ER) or isolated under impoverished (IR) environmental conditions. Bromodeoxyuridine (BrdU) labeling was in young adults (90 days postpartum, pp 90), and animals survived 1 day, 1 week or 6 weeks, in order-to separate short-term cell proliferation from long-term survival rates of the progeny. The cell proliferation proved. to be significantly elevated in the IR as compared with the ER group in 1 week post-labelings, and attained similar low values in the 6 week survivals. No useful data could be obtained from the 1 day survivors because of clustering. Lysosomal accumulation (LA) in degrading synapses was quantified at pp 90 in selected fields of the hippocampal gyrus dentatus, of both ER and IR specimens. LA was significantly lowered in all molecular layers along the septo-temporal hippocampal axis of the IR as compared with the ER group, which indicates a reduced synapse remodeling under IR conditions. Results suggest that IR conditions during peri- and postnatal life cause morphogenetic effects that interfere with neurogenesis and synaptogenesis throughout life. Based on our results, recent publications on experience induced elevations and stress induced suppression of neurogenesis in the mammalian hippocampus demand a reinterpretation in view of the fact that rearing conditions set brain predispositions for life

<span style="font-size: 21.5pt;mso-bidi-font-size:14.5pt;font-family:"Times New Roman","serif"">Electromagnetic exposure effects the hippocampal dentate cell proliferation in gerbils <i>(Meriones unguiculatus)</i> </span>

1220-1226<span style="font-size: 16.0pt;mso-bidi-font-size:9.0pt;font-family:" times="" new="" roman","serif""="">The chronic effect on hippocampal neurogenesis after exposure (30 min/day for 14 days) to a high frequency (35,53 kHz) electromagnetic field, double modulated at extremely low frequencies (ELF; 1, 8, 12, 29 and 50 Hz), was studied in young adult gerbils. Immediately after the last exposure proliferation of dentate granule cells was identified by in vivo labeling with 5-bromo-2-desoxyuridine (BrdU). Exposure to 1, 29 and 50 <span style="font-size:16.0pt; mso-bidi-font-size:9.0pt;font-family:" times="" new="" roman","serif""="">Hz resulted in a statistically significant reduction of cell proliferation rates, but only the 50Hz-group manifested the effect highly significantly (-29,3 %). On the other hand, gerbils exposed to 8 and 12 Hz showed no significant change of postmitotic cell proliferation as compared with the sham treated controls. The results suggest that the effects of ELF on the granule cell proliferation are mediated by neurotmnsmitters and hormones which regulate hippocampal neurogenesis. </span

Electromagnetic exposure effects the hippocampal dentate cell proliferation in gerbils (Meriones unguiculatus)

Hoffmann K, Bagorda F, Stevenson AF, Teuchert-Noodt G. Electromagnetic exposure effects the hippocampal dentate cell proliferation in gerbils (Meriones unguiculatus). Indian J Exp Biol. 2001;39(12):1220-1226.The chronic effect on hippocampal neurogenesis after exposure (30 min/day for 14 days) to a high frequency (35,53 kHz) electromagnetic field, double modulated at extremely low frequencies (ELF; 1, 8, 12, 29 and 50 Hz), was studied in young adult gerbils. Immediately after the last exposure proliferation of dentate granule cells was identified by in vivo labeling with 5-bromo-2-desoxyuridine (BrdU). Exposure to 1, 29 and 50 Hz resulted in a statistically significant reduction of cell proliferation rates, but only the 50 Hz-group manifested the effect highly significantly (-29,3 %). On the other hand, gerbils exposed to 8 and 12 Hz showed no significant change of postmitotic cell proliferation as compared with the sham treated controls. The results suggest that the effects of ELF on the granule cell proliferation are mediated by neurotransmitters and hormones which regulate hippocampal neurogenesis