scholarly journals Topographic cell instructive patterns to control cell adhesion, polarization and migration

2014 ◽  
Vol 11 (100) ◽  
pp. 20140687 ◽  
Author(s):  
Maurizio Ventre ◽  
Carlo Fortunato Natale ◽  
Carmela Rianna ◽  
Paolo Antonio Netti

Topographic patterns are known to affect cellular processes such as adhesion, migration and differentiation. However, the optimal way to deliver topographic signals to provide cells with precise instructions has not been defined yet. In this work, we hypothesize that topographic patterns may be able to control the sensing and adhesion machinery of cells when their interval features are tuned on the characteristic lengths of filopodial probing and focal adhesions (FAs). Features separated by distance beyond the length of filopodia cannot be readily perceived; therefore, the formation of new adhesions is discouraged. If, however, topographic features are separated by a distance within the reach of filopodia extension, cells can establish contact between adjacent topographic islands. In the latter case, cell adhesion and polarization rely upon the growth of FAs occurring on a specific length scale that depends on the chemical properties of the surface. Topographic patterns and chemical properties may interfere with the growth of FAs, thus making adhesions unstable. To test this hypothesis, we fabricated different micropatterned surfaces displaying feature dimensions and adhesive properties able to interfere with the filopodial sensing and the adhesion maturation, selectively. Our data demonstrate that it is possible to exert a potent control on cell adhesion, elongation and migration by tuning topographic features’ dimensions and surface chemistry.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
W. Tucker Shelton ◽  
S. Madison Thomas ◽  
Hunter R. Alexander ◽  
C. Evan Thomes ◽  
Daniel E. Conway ◽  
...  

AbstractDesmosomes have a central role in mediating extracellular adhesion between cells, but they also coordinate other biological processes such as proliferation, differentiation, apoptosis and migration. In particular, several lines of evidence have implicated desmosomal proteins in regulating the actin cytoskeleton and attachment to the extracellular matrix, indicating signaling crosstalk between cell–cell junctions and cell–matrix adhesions. In our study, we found that cells lacking the desmosomal cadherin Desmoglein-2 (Dsg2) displayed a significant increase in spreading area on both fibronectin and collagen, compared to control A431 cells. Intriguingly, this effect was observed in single spreading cells, indicating that Dsg2 can exert its effects on cell spreading independent of cell–cell adhesion. We hypothesized that Dsg2 may mediate cell–matrix adhesion via control of Rap1 GTPase, which is well known as a central regulator of cell spreading dynamics. We show that Rap1 activity is elevated in Dsg2 knockout cells, and that Dsg2 harnesses Rap1 and downstream TGFβ signaling to influence both cell spreading and focal adhesion protein phosphorylation. Further analysis implicated the Rap GEF PDZ-GEF2 in mediating Dsg2-dependent cell spreading. These data have identified a novel role for Dsg2 in controlling cell spreading, providing insight into the mechanisms via which cadherins exert non-canonical junction-independent effects.


2003 ◽  
Vol 807 ◽  
Author(s):  
Haruo Sato

ABSTRACTIn-diffusion experiments for Cs+ and I− in sandstone were performed as a function of ionic strength ([NaCl]=0.01, 0.51M) and tracer concentration ([CsI]=7.5E-5, 1.5E-2M) together with the measurements of the physical and chemical properties of sandstone, and apparent diffusivities (Da) for Cs+ were obtained. The obtained Da-values for Cs+ scarcely depended on [NaCl], but increased with increasing [Cs+]. This trend is consistent with that of rock capacity factors (α), indicating that distribution coefficient (Kd) onto sandstone and effective diffusivity scarcely depend on [NaCl]. The concentration profiles of I− were all in already breakthrough. Although this indicates that I− diffusion is faster than that of Cs+, the concentration profiles of I− may have been lower than those for blank samples, judging synthetically from the correlations between α-values and the concentration profiles of Cs+ and from the concentration profiles of I− in the blank samples. Finally, the effects of [Cs+] and[NaCl] on Kd/-values for Cs+ were discussed from the viewpoint of adsorption by ion exchange and electrostatic attraction. The kd-values were considered to be combined sorption by both reactions.


2009 ◽  
Vol 186 (3) ◽  
pp. 423-436 ◽  
Author(s):  
Sabina E. Winograd-Katz ◽  
Shalev Itzkovitz ◽  
Zvi Kam ◽  
Benjamin Geiger

Cell adhesion to the extracellular matrix is mediated by elaborate networks of multiprotein complexes consisting of adhesion receptors, cytoskeletal components, signaling molecules, and diverse adaptor proteins. To explore how specific molecular pathways function in the assembly of focal adhesions (FAs), we performed a high-throughput, high-resolution, microscopy-based screen. We used small interfering RNAs (siRNAs) to target human kinases, phosphatases, and migration- and adhesion-related genes. Multiparametric image analysis of control and of siRNA-treated cells revealed major correlations between distinct morphological FA features. Clustering analysis identified different gene families whose perturbation induced similar effects, some of which uncoupled the interfeature correlations. Based on these findings, we propose a model for the molecular hierarchy of FA formation, and tested its validity by dynamic analysis of FA formation and turnover. This study provides a comprehensive information resource on the molecular regulation of multiple cell adhesion features, and sheds light on signaling mechanisms regulating the formation of integrin adhesions.


2011 ◽  
Vol 13 (10) ◽  
pp. B395-B404 ◽  
Author(s):  
Mar Diez ◽  
Vera A. Schulte ◽  
Filippo Stefanoni ◽  
Carlo F. Natale ◽  
Francesco Mollica ◽  
...  

e-Polymers ◽  
2014 ◽  
Vol 14 (5) ◽  
pp. 297-304
Author(s):  
Guo-xun Chang ◽  
Ke-feng Ren ◽  
Yi-xiu Zhao ◽  
Yi-xin Sun ◽  
Jian Ji

AbstractIn addition to the topographical features and chemical properties of substrates, the mechanical properties are known as a vital regulator of cellular processes such as adhesion, proliferation, and migration, and have received considerable attention in recent years. In this work, electrochemical redox multilayers made of ferrocene-modified poly(ethylenimine) (PEI-Fc) and deoxyribonucleic acid (DNA) with controlled stiffness were used to investigate the effects of the mechanical properties of multilayers on fibroblast cell (NIH/3T3) behaviors. Redox PEI-Fc plays an essential role in inducing swelling in multilayers under an electrochemical stimulus, resulting in distinct changes in the stiffness of the multilayers. The Young’s modulus varied from 2.05 to 1.07 MPa for the (PEI-Fc/DNA) multilayers by changing the oxidation time of the electrochemical treatment. We demonstrated that the adhesion, proliferation, and migration of fibroblast cells depended on the multilayers’ stiffness. These results indicate that cell behaviors can be precisely controlled by electrochemical treatment, which provides a new way to prepare thin films with tunable mechanical properties with potential biomedical applications.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Freda Passam ◽  
Joyce Chiu ◽  
Lining Ju ◽  
Aster Pijning ◽  
Zeenat Jahan ◽  
...  

How proteins harness mechanical force to control function is a significant biological question. Here we describe a human cell surface receptor that couples ligand binding and force to trigger a chemical event which controls the adhesive properties of the receptor. Our studies of the secreted platelet oxidoreductase, ERp5, have revealed that it mediates release of fibrinogen from activated platelet αIIbβ3 integrin. Protein chemical studies show that ligand binding to extended αIIbβ3 integrin renders the βI-domain Cys177-Cys184 disulfide bond cleavable by ERp5. Fluid shear and force spectroscopy assays indicate that disulfide cleavage is enhanced by mechanical force. Cell adhesion assays and molecular dynamics simulations demonstrate that cleavage of the disulfide induces long-range allosteric effects within the βI-domain, mainly affecting the metal-binding sites, that results in release of fibrinogen. This coupling of ligand binding, force and redox events to control cell adhesion may be employed to regulate other protein-protein interactions.


2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Evgenia Uglova ◽  
Eugene Eremenko ◽  
Natalya Sikachyova ◽  
Kiril Kuzin

To increase the adhesion strength (wetting ability) of bitumen, and, consequently, reduce the likelihood of premature occurrence of defects formed on asphalt concrete coatings, it is necessary to use various kinds of surfactants that increase the adhesion ability of bitumen. Adhesive additives to road bitumens increase the mobility of the organic binder, help reduce the number of uncoated grains of mineral material, which facilitates the compaction of asphalt concrete mix. One of the problems of durability of asphalt concrete pavements is the lack of strong adhesion of the bitumen film to the surface of the mineral material. To increase this strength, various adhesive additives are used, which affect not only the adhesive properties of bitumen, but also its physical and chemical properties. The main task of the work is aimed at solving the issues of the influence of adhesive additives on the physicochemical properties of organic binders used in road construction. The quality assessment of the modified bitumen was carried out according to GOST 22245-90, which, at present, is guided by the selection of the composition of the asphalt concrete mixture. As a result of the study, effective adhesive additives were identified that contribute to the minimal change in the physicochemical properties of viscous road bitumen and possess thermal stability under prolonged exposure to elevated temperatures. Studies have shown that almost all adhesive additives not only improve the adhesive properties of organic binders to mineral materials, but also can alter and even worsen the physicochemical properties of the original organic binder, which can adversely affect the properties of asphalt concrete. The study used the original bitumen from only one manufacturer and the negative effect of adhesive additives may be due to the incompatible chemical composition of the adhesive additive with the group composition of bitumen and the mineralogical composition of the mineral material.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zlata Vershinin ◽  
Michal Feldman ◽  
Dan Levy

Abstract P21-activated kinase 4 (PAK4), a member of serine/threonine kinases family is over-expressed in numerous cancer tumors and is associated with oncogenic cell proliferation, migration and invasion. Our recent work demonstrated that the SET-domain containing protein 6 (SETD6) interacts with and methylates PAK4 at chromatin in mammalian cells, leading to activation of the Wnt/β-catenin signaling pathway. In our current work, we identified lysine 473 (K473) on PAK4 as the primary methylation site by SETD6. Methylation of PAK4 at K473 activates β-catenin transcriptional activity and inhibits cell adhesion. Specific methylation of PAK4 at K473 also attenuates paxillin localization to focal adhesions leading to overall reduction in adhesion-related features, such as filopodia and actin structures. The altered adhesion of the PAK4 wild-type cells is accompanied with a decrease in the migrative and invasive characteristics of the cells. Taken together, our results suggest that methylation of PAK4 at K473 plays a vital role in the regulation of cell adhesion and migration.


2018 ◽  
Vol 8 (2) ◽  
pp. 230-242
Author(s):  
Vyacheslav Polyakov ◽  
Alina Petrova ◽  
Alexander Kozlov ◽  
Evgeny Abakumov

Nowadays, active urbanization directly affects to the transformation of natural ecosystems in all natural zones of Russian Federation. First of all, soils of the cities are exposed to undergoing to intensive transformation. With this transformation, natural soils change to urban and “urbo-natural soils”. Arctic ecosystems are most susceptible to anthropogenic influence because they have a low regeneration and restoration ability. Urban soils demonstrate numerous and various processes of transformation and migration of substances, which are the most important links in the biogeochemical cycles, linking the various structural components of ecosystems and the biosphere as a whole. In this context the processes of soils transformation under the influence of the urbanization has been considered. Soils of residential, recreational (park), industrial and non-developed urban zones were studied on example of Murmansk city as one on the northernmost city in European part of Russia. Microbiological activities, toxicological state (heavy metals, Zc), and content of carbon in soils were revealed.


2011 ◽  
Vol 22 (21) ◽  
pp. 4047-4058 ◽  
Author(s):  
Tina M. Bunnell ◽  
Brandon J. Burbach ◽  
Yoji Shimizu ◽  
James M. Ervasti

Ubiquitously expressed β-actin and γ-actin isoforms play critical roles in most cellular processes; however, their unique contributions are not well understood. We generated whole-body β-actin–knockout (Actb−/−) mice and demonstrated that β-actin is required for early embryonic development. Lethality of Actb−/−embryos correlated with severe growth impairment and migration defects in β-actin–knockout primary mouse embryonic fibroblasts (MEFs) that were not observed in γ-actin–null MEFs. Migration defects were associated with reduced membrane protrusion dynamics and increased focal adhesions. We also identified migration defects upon conditional ablation of β-actin in highly motile T cells. Of great interest, ablation of β-actin altered the ratio of globular actin (G-actin) to filamentous actin in MEFs, with corresponding changes in expression of genes that regulate the cell cycle and motility. These data support an essential role for β-actin in regulating cell migration and gene expression through control of the cellular G-actin pool.


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