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Substrate Topography Determines Neuronal Polarization and Growth In Vitro  [PDF]
Liesbeth Micholt, Annette G?rtner, Dimiter Prodanov, Dries Braeken, Carlos G. Dotti, Carmen Bartic
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066170
Abstract: The establishment of neuronal connectivity depends on the correct initial polarization of the young neurons. In vivo, developing neurons sense a multitude of inputs and a great number of molecules are described that affect their outgrowth. In vitro, many studies have shown the possibility to influence neuronal morphology and growth by biophysical, i.e. topographic, signaling. In this work we have taken this approach one step further and investigated the impact of substrate topography in the very early differentiation stages of developing neurons, i.e. when the cell is still at the round stage and when the first neurite is forming. For this purpose we fabricated micron sized pillar structures with highly reproducible feature sizes, and analyzed neurons on the interface of flat and topographic surfaces. We found that topographic signaling was able to attract the polarization markers of mouse embryonic neurons -N-cadherin, Golgi-centrosome complex and the first bud were oriented towards topographic stimuli. Consecutively, the axon was also preferentially extending along the pillars. These events seemed to occur regardless of pillar dimensions in the range we examined. However, we found differences in neurite length that depended on pillar dimensions. This study is one of the first to describe in detail the very early response of hippocampal neurons to topographic stimuli.
Osteopontin’s colocalization with the adhesion molecule CEACAM5 in cytoplasm of carcinoma of tongue and its correlation with the invasion of that diease
Fan Zhang, Xu Jin Liu, Xun Qu, Zhen Sheng Hu, Yong Mei Yang, Ling Ma, Pei Liu, Ping Shi, Feng Cai Wei
Cancer Cell International , 2012, DOI: 10.1186/1475-2867-12-33
Abstract: Paraffin were sections of 80 samples with squamous carcinoma of tongue and 40 samples with normal tissue of tongue for benign lesion having undergone surgery. Immunohistochemistry (IHC) was used to study the distribution of CEACAM5 and OPN, and double–labeling immunohistochemistry was used to observe the relationship between CEACAM5 and OPN expression.CEACAM5 and OPN are found in normal tissue of tongue, but with different expression pattern. CEACAM5 expression mainly with membranous staining is restricted on the superficial epithelium. However, OPN expression with mainly cytoplasmic staining is restricted on the deep epithelium. No colocalization of CEACAM5 and OPN have been observed in normal tissue of tongue. In squamous carcinoma of tongue, CEACAM5 expression with cytoplasmic staining is different from normal tongue tissue with membranous staining, and the transformation of CEACAM5 distribution from membrane to cytoplasm is an important incident for the invasion and differentiation of tumor. CEACAM5 and OPN are colocalized in cytoplasm, and a significant correlation was observed between the positive colocalization and the negative colocalization in the depth of invasion and the differentiation of the tumor.Homeostasis in normal tissue is regulated by a balance between proliferative activity and cell loss by apoptosis [1,2]. Attachment to correct extracellular matrix (ECM) is essential for survival and growth of normal adhering cells, whereas cancer cells are able to abrogate this requirement. Several growth factors and cytokines play pivotal roles in the regulation of growth and survival of neoplastic cells through affecting integrin-mediated adhesion to ECM.Cell adhesion molecules are important mediators of cellular contacts and cellular polarity that also modulate proliferation, differentiation, and invasion. Osteopontin (OPN) is a 70-kDa secreted extracellular matrix glycoprotein with an arginine-glycine aspartate-binding motif capable of interaction with int
Wet Adhesion and Adhesive Locomotion of Snails on Anti-Adhesive Non-Wetting Surfaces  [PDF]
Neil J. Shirtcliffe, Glen McHale, Michael I. Newton
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036983
Abstract: Creating surfaces capable of resisting liquid-mediated adhesion is extremely difficult due to the strong capillary forces that exist between surfaces. Land snails use this to adhere to and traverse across almost any type of solid surface of any orientation (horizontal, vertical or inverted), texture (smooth, rough or granular) or wetting property (hydrophilic or hydrophobic) via a layer of mucus. However, the wetting properties that enable snails to generate strong temporary attachment and the effectiveness of this adhesive locomotion on modern super-slippy superhydrophobic surfaces are unclear. Here we report that snail adhesion overcomes a wide range of these microscale and nanoscale topographically structured non-stick surfaces. For the one surface which we found to be snail resistant, we show that the effect is correlated with the wetting response of the surface to a weak surfactant. Our results elucidate some critical wetting factors for the design of anti-adhesive and bio-adhesion resistant surfaces.
Influence of microenvironment on cell adhesion, polarization, and migration
Pajic-Lijakovic I, Plavsic M
International Journal of Nanomedicine , 2012, DOI: http://dx.doi.org/10.2147/IJN.S33433
Abstract: Influence of microenvironment on cell adhesion, polarization, and migration Letter (2717) Total Article Views Authors: Pajic-Lijakovic I, Plavsic M Published Date July 2012 Volume 2012:7 Pages 3473 - 3474 DOI: http://dx.doi.org/10.2147/IJN.S33433 Received: 30 April 2012 Accepted: 03 May 2012 Published: 06 July 2012 Ivana Pajic-Lijakovic, Milenko Plavsic Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia We read an interesting article by Torres-Costa et al1 recently published in the International Journal of Nanomedicine. The influence of the rheological behavior of extracellular matrix (ECM) to cell adhesion and migration represents an important issue for various biomedical applications. The nature of cell adhesion and migration are stochastic as reported by Stokes et al.2 Cell migration should be considered in subcellular and cellular levels by applying fluctuation-dissipation theorem in the form of Langevin-type force-balance equations,3–5 and supercellular level by formulating mesoscopic mass and stress-balance equations.6 View the original article by Torres-Costa and colleagues. Post to: Cannotea Citeulike Del.icio.us Facebook LinkedIn Twitter Readers of this article also read: Intercellular cancer collisions generate an ejected crystal comet tail effect with fractal interface embryoid body reassembly transformation Enhancing cellular uptake of activable cell-penetrating peptide–doxorubicin conjugate by enzymatic cleavage Multi-dye theranostic nanoparticle platform for bioimaging and cancer therapy Optical imaging to trace near infrared fluorescent zinc oxide nanoparticles following oral exposure Lipid-based liquid crystalline nanoparticles as oral drug delivery vehicles for poorly water-soluble drugs: cellular interaction and in vivo absorption Critical appraisal of bevacizumab in the treatment of metastatic colorectal cancer Post intrastromal corneal ring segments insertion complicated by Candida parapsilosis keratitis Cancer stem cell theory: therapeutic implications for nanomedicine What are the roles of carers in decision-making for amyotrophic lateral sclerosis multidisciplinary care? Oral biofilms: molecular analysis, challenges, and future prospects in dental diagnostics
Synthetic spatially graded Rac activation drives directed cell polarization and locomotion  [PDF]
Benjamin Lin,William R. Holmes,ChiaoChun Wang,Tasuku Ueno,Andrew Harwell,Leah Edelstein-Keshet,Takanari Inoue,Andre Levchenko and
Quantitative Biology , 2012, DOI: 10.1073/pnas.1210295109
Abstract: Migrating cells possess intracellular gradients of Rho GTPases, but it is unknown whether these shallow gradients themselves can induce motility. Here we describe a new method to present cells with induced linear gradients of active, endogenous Rac without receptor activation. Gradients as low as 15% were sufficient to not only trigger cell migration up the synthetic gradient, but also to induce both cell polarization and repolarization. Response kinetics were inversely proportional to Rac gradient values, in agreement with a new mathematical model, suggesting a role for natural input gradient amplification upstream of Rac. Increases in Rac levels beyond a well-defined threshold dramatically augmented polarization and decreased sensitivity to the gradient value. The threshold was governed by initial cell polarity and PI3K activity, supporting a role for both in defining responsiveness to natural or synthetic Rac activation. Our methodology suggests a general way to investigate processes regulated by intracellular signaling gradients.
Dcas Supports Cell Polarization and Cell-Cell Adhesion Complexes in Development  [PDF]
Nadezhda Tikhmyanova,Alexei V. Tulin,Fabrice Roegiers,Erica A. Golemis
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012369
Abstract: Mammalian Cas proteins regulate cell migration, division and survival, and are often deregulated in cancer. However, the presence of four paralogous Cas family members in mammals (BCAR1/p130Cas, EFS/Sin1, NEDD9/HEF1/Cas-L, and CASS4/HEPL) has limited their analysis in development. We deleted the single Drosophila Cas gene, Dcas, to probe the developmental function of Dcas. Loss of Dcas had limited effect on embryonal development. However, we found that Dcas is an important modulator of the severity of the developmental phenotypes of mutations affecting integrins (If and mew) and their downstream effectors Fak56D or Src42A. Strikingly, embryonic lethal Fak56D-Dcas double mutant embryos had extensive cell polarity defects, including mislocalization and reduced expression of E-cadherin. Further genetic analysis established that loss of Dcas modified the embryonal lethal phenotypes of embryos with mutations in E-cadherin (Shg) or its signaling partners p120- and β-catenin (Arm). These results support an important role for Cas proteins in cell-cell adhesion signaling in development.
Formin 1-Isoform IV Deficient Cells Exhibit Defects in Cell Spreading and Focal Adhesion Formation  [PDF]
Markus Dettenhofer, Fen Zhou, Philip Leder
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002497
Abstract: Background Regulation of the cytoskeleton is a central feature of cell migration. The formin family of proteins controls the rate of actin nucleation at its barbed end. Thus, formins are predicted to contribute to several important cell processes such as locomotion, membrane ruffling, vesicle endocytosis, and stress fiber formation and disassociation. Methodology/Principal Findings In this study we investigated the functional role of Formin1-isoform4 (Fmn1-IV) by using genetically null primary cells that displayed augmented protrusive behaviour during wound healing and delayed cell spreading. Cells deficient of Fmn1-IV also showed reduced efficiency of focal adhesion formation. Additionally, we generated an enhanced green fluorescence protein (EGFP)-fused Fmn1-IV knock-in mouse to monitor the endogenous subcellular localization of Fmn1-IV. Its localization was found within the cytoplasm and along microtubules, yet it was largely excluded from adherens junctions. Conclusions/Significance It was determined that Fmn1-IV, as an actin nucleator, contributes to protrusion of the cell's leading edge and focal adhesion formation, thus contributing to cell motility.
Undulatory Locomotion  [PDF]
Netta Cohen,Jordan H. Boyle
Physics , 2009,
Abstract: Undulatory locomotion is a means of self-propulsion that relies on the generation and propagation of waves along a body. As a mode of locomotion it is primitive and relatively simple, yet can be remarkably robust. No wonder then, that it is so prevalent across a range of biological scales from motile bacteria to gigantic prehistoric snakes. Key to understanding undulatory locomotion is the body's interplay with the physical environment, which the swimmer or crawler will exploit to generate propulsion, and in some cases, even to generate the underlying undulations. This review focuses by and large on undulators in the low Reynolds numbers regime, where the physics of the environment can be much more tractable. We review some key concepts and theoretical advances, as well as simulation tools and results applied to selected examples of biological swimmers. In particular, we extend the discussion to some simple cases of locomotion in non-Newtonian media as well as to small animals, in which the nervous system, motor control, body properties and the environment must all be considered to understand how undulations are generated and modulated. To conclude, we review recent progress in microrobotic undulators that may one day become commonplace in applications ranging from toxic waste disposal to minimally invasive surgery.
Cortical Factor Feedback Model for Cellular Locomotion and Cytofission  [PDF]
Shin I. Nishimura ,Masahiro Ueda,Masaki Sasai
PLOS Computational Biology , 2009, DOI: 10.1371/journal.pcbi.1000310
Abstract: 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.
The Composition and Organization of Cytoplasm in Prebiotic?Cells  [PDF]
Jack T. Trevors
International Journal of Molecular Sciences , 2011, DOI: 10.3390/ijms12031650
Abstract: This article discusses the hypothesized composition and organization of cytoplasm in prebiotic cells from a theoretical perspective and also based upon what is currently known about bacterial cytoplasm. It is unknown if the first prebiotic, microscopic scale, cytoplasm was initially contained within a primitive, continuous, semipermeable membrane, or was an uncontained gel substance, that later became enclosed by a continuous membrane. Another possibility is that the first cytoplasm in prebiotic cells and a primitive membrane organized at the same time, permitting a rapid transition to the first cell(s) capable of growth and division, thus assisting with the emergence of life on Earth less than a billion years after the formation of the Earth. It is hypothesized that the organization and composition of cytoplasm progressed initially from an unstructured, microscopic hydrogel to a more complex cytoplasm, that may have been in the volume magnitude of about 0.1–0.2 μm 3 (possibly less if a nanocell) prior to the first cell division.
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