Cortical Factor Feedback Model for Cellular Locomotion and Cytofission

Eukaryotic cells can move spontaneously without being guided by external cues. For such spontaneous movements, a variety of different modes have been observed, including the amoeboid-like locomotion with protrusion of multiple pseudopods, the keratocyte-like locomotion with a widely spread lamellipodium, cell division with two daughter cells crawling in opposite directions, and fragmentations of a cell to multiple pieces. Mutagenesis studies have revealed that cells exhibit these modes depending on which genes are deficient, suggesting that seemingly different modes are the manifestation of a common mechanism to regulate cell motion. In this paper, we propose a hypothesis that the positive feedback mechanism working through the inhomogeneous distribution of regulatory proteins underlies this variety of cell locomotion and cytofission. In this hypothesis, a set of regulatory proteins, which we call cortical factors, suppress actin polymerization. These suppressing factors are diluted at the extending front and accumulated at the retracting rear of cell, which establishes a cellular polarity and enhances the cell motility, leading to the further accumulation of cortical factors at the rear. Stochastic simulation of cell movement shows that the positive feedback mechanism of cortical factors stabilizes or destabilizes modes of movement and determines the cell migration pattern. The model predicts that the pattern is selected by changing the rate of formation of the actin-filament network or the threshold to initiate the network formation

Self-Regulation of Breathing as a Primary Treatment for Anxiety

Understanding the autonomic nervous system and homeostatic changes associated with emotions remains a major challenge for neuroscientists and a fundamental prerequisite to treat anxiety, stress, and emotional disorders. Based on recent publications, the inter-relationship between respiration and emotions and the influence of respiration on autonomic changes, and subsequent widespread membrane potential changes resulting from changes in homeostasis are discussed. We hypothesize that reversing homeostatic alterations with meditation and breathing techniques rather than targeting neurotransmitters with medication may be a superior method to address the whole body changes that occur in stress, anxiety, and depression. Detrimental effects of stress, negative emotions, and sympathetic dominance of the autonomic nervous system have been shown to be counteracted by different forms of meditation, relaxation, and breathing techniques. We propose that these breathing techniques could be used as firstline and supplemental treatments for stress, anxiety, depression, and some emotional disorders

Bridging from single to collective cell migration: A review of models and links to experiments

Mathematical and computational models can assist in gaining an understanding of cell behavior at many levels of organization. Here, we review models in the literature that focus on eukaryotic cell motility at 3 size scales: intracellular signaling that regulates cell shape and movement, single cell motility, and collective cell behavior from a few cells to tissues. We survey recent literature to summarize distinct computational methods (phase-field, polygonal, Cellular Potts, and spherical cells). We discuss models that bridge between levels of organization, and describe levels of detail, both biochemical and geometric, included in the models. We also highlight links between models and experiments. We find that models that span the 3 levels are still in the minority.Comment: 39 pages, 5 figure

The Role of Intracellular Interactions in the Collective Polarization of Tissues and its Interplay with Cellular Geometry

Planar cell polarity (PCP), the coherent in-plane polarization of a tissue on multicellular length scales, provides directional information that guides a multitude of developmental processes at cellular and tissue levels. While it is manifest that cells utilize both intracellular and intercellular mechanisms, how the two produce the collective polarization remains an active area of investigation. We study the role of intracellular interactions in the large-scale spatial coherence of cell polarities, and scrutinize the role of intracellular interactions in the emergence of tissue-wide polarization. We demonstrate that nonlocal cytoplasmic interactions are necessary and sufficient for the robust long-range polarization, and are essential to the faithful detection of weak directional signals. In the presence of nonlocal interactions, signatures of geometrical information in tissue polarity become manifest. We investigate the deleterious effects of geometric disorder, and determine conditions on the cytoplasmic interactions that guarantee the stability of polarization. These conditions get progressively more stringent upon increasing the geometric disorder. Another situation where the role of geometrical information might be evident is elongated tissues. Strikingly, our model recapitulates an observed influence of tissue elongation on the orientation of polarity. Eventually, we introduce three classes of mutants: lack of membrane proteins, cytoplasmic proteins, and local geometrical irregularities. We adopt core-PCP as a model pathway, and interpret the model parameters accordingly, through comparing the in silico and in vivo phenotypes. This comparison helps us shed light on the roles of the cytoplasmic proteins in cell-cell communication, and make predictions regarding the cooperation of cytoplasmic and membrane proteins in long-range polarization.Comment: 15 pages Main Text + 8 page Appendi

Multiple Feedback Mechanisms Fine-Tune Rho Signaling To Regulate Morphogenetic Outcomes

Rho signaling is a conserved mechanism for generating forces through activation of contractile actomyosin. How this pathway is tuned to produce different morphologies of cells and tissues is poorly understood. In the Drosophila embryonic epithelium, I investigated how Rho signaling controls force asymmetries to drive morphogenesis. Specifically, I studied a distinctive morphogenetic process termed “alignment”. This process of coordinated cell shape changes results in a unique cell geometry of rectilinear cells connected by aligned cell-cell contacts. I found that this rearrangement is initialized by contractility of actomyosin cables that elevate the local tension along aligning interfaces. Curiously, I find that hours after establishing the alignment, this cell geometry is stabilized independent of actomyosin at the end of embryogenesis. This suggests that there are alternate mechanical bases for maintaining the aligned cell geometry in the steady state. My data show that polarization of two branches of Rho signaling, Rho Kinase (ROK) and Diaphanous (Dia), is responsible for the formation of these cables. Constitutive activation of these Rho effectors causes aligning cells to instead invaginate. This observation suggests that moderation of Rho signaling is essential to producing the aligned geometry. Therefore, I tested for feedback interactions in the pathway that could fine-tune Rho signaling. I discovered that F-actin exerts negative feedback on multiple nodes in the pathway. In contrast, Myo-II does not feedback to the Rho pathway. However, inhibiting ROK caused an upregulation in Rho activity. This shows that ROK has a Myo-II independent function in regulating the Rho pathway. Taken together, this work suggests that multiple feedback mechanisms factor into the regulation of Rho signaling, which may account for the versatility of Rho in diverse morphogenetic processes. Preliminarily, I also find a requirement for a regulator of Rac-Arp 2/3-mediated actin polymerization, pointing towards cooperation and crosstalk between branched actin and linear actin promoting pathways. This may allow for a balance of different mechanical forces that can generate the aligned geometry. This thesis work lays down a foundation for understanding how the activity of contractile actomyosin and small GTPase signaling be modified to suit numerous morphogenetic processes

Exploring Nanoscale Organisation of Synapses with Super-Resolution Microscopy

The rapid advance of super-resolution microscopy and its experimental applications has provided neuroscientists with a pass to the nanoscopic world of synaptic machinery. Here we will briefly overview and discuss current progress in our understanding of the three-dimensional synaptic architecture and molecular organisation as gleaned from the imaging methods that go beyond the diffraction limit of conventional light microscopy. We will argue that such methods are to take our knowledge of synapses to a qualitatively new level, providing the neuroscience research community with novel organising principles and concepts pertinent to the workings of the brain

Studies on the stimulation of Atlantic salmon macrophage-like cells with emphasis on respiratory burst

Reactive oxygen species (ROS) production in macrophage-like cells is induced as an antimicrobial defence against invading pathogens. In this present study, we have explored how different stimuli and metabolic inhibitors affects the level of respiratory burst in Atlantic salmon (Salmo salar L.) head kidney macrophage-like cells. Cells stimulated in vitro by bacterial lipopolysaccharide (LPS) and ß-glucan showed increased production of ROS compared to unstimulated cells. Both stimulation and co-stimulation by curdlan (ß-glucan) induced a higher production of ROS compared to stimulation and co-stimulation by LPS. Metabolic inhibitors (developed for mammals) co-incubated with the stimulants did not, in most cases, perturb the level of ROS generation in the salmon macrophage-like cells. The NAD+ content as well as the NAD+/NADH ratio increased in curdlan, and LPS + curdlan stimulated cells compared to control cells, which indicated increased metabolic activity in the stimulated cells. Supporting these findings, gene analysis using SYBR green real-time quantitative PCR showed that the genes Arignase-1 and IL-1ß were highly expressed in the stimulated cells