scholarly journals Transepithelial potential difference governs epithelial homeostasis by electromechanics

2021 ◽  
Author(s):  
Thuan Beng Saw ◽  
Xumei Gao ◽  
Jianan He ◽  
Anh Phuong Le ◽  
Supatra Marsh ◽  
...  
Keyword(s):  
Limb Regeneration ◽  
Hydrodynamic Theory ◽  
Epithelial Layer ◽  
Knock Out ◽  
Substrate Adhesion ◽  
Epithelial Homeostasis ◽  
Long Time ◽  
Cell Shapes ◽  
Cell Substrate Adhesion ◽  
Electric Effects

Abstract Studies of electric effects in biological systems, from the historical experiments of Galvani 1 and the ground-breaking work on action potential2 to studies on limb regeneration3 or wound healing4, share the common feature of being concerned with transitory behavior and not addressing the question of homeostasis. Here using a novel microfluidic device, we study how the homeostasis of confluent epithelial tissues is modified when a trans-epithelial electric potential (TEPD) different from the natural one is imposed on an epithelial layer. We show that epithelial fate is dependent on TEPD of few Volts/cm similar to the endogenous one. When the field direction matches the natural one, we can restore a perfect confluence in an epithelial layer turned defective either by E-cadherin knock-out or by weakening cell-substrate adhesion; additionally, the tissue pushes on the substrate with kilo-Pascals stress, inducing active cell response such as death and differentiation. When the field is opposite, homeostasis is destroyed by the perturbation of junctional actin and cell shapes, and the formation of dynamical mounds5, while the tissue pulls with similar strengths. Most of these observations can be quantitatively explained by an electro-hydrodynamic theory involving local electro-osmotic flows. We expect this work to motivate further studies on long time effects of electromechanical pathways with important tissue engineering applications.

scholarly journals The interplay of cell–cell and cell–substrate adhesion in collective cell migration

2014 ◽  
Vol 11 (100) ◽  
pp. 20140684 ◽  
Author(s):  
Chenlu Wang ◽  
Sagar Chowdhury ◽  
Meghan Driscoll ◽  
Carole A. Parent ◽  
S. K. Gupta ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Actin Polymerization ◽  
Collective Cell Migration ◽  
Cell Contacts ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Shapes ◽  
Cell Substrate Adhesion ◽  
Cell Cell

Collective cell migration often involves notable cell–cell and cell–substrate adhesions and highly coordinated motion of touching cells. We focus on the interplay between cell–substrate adhesion and cell–cell adhesion. We show that the loss of cell-surface contact does not significantly alter the dynamic pattern of protrusions and retractions of fast migrating amoeboid cells ( Dictyostelium discoideum ), but significantly changes their ability to adhere to other cells. Analysis of the dynamics of cell shapes reveals that cells that are adherent to a surface may coordinate their motion with neighbouring cells through protrusion waves that travel across cell–cell contacts. However, while shape waves exist if cells are detached from surfaces, they do not couple cell to cell. In addition, our investigation of actin polymerization indicates that loss of cell-surface adhesion changes actin polymerization at cell–cell contacts. To further investigate cell–cell/cell–substrate interactions, we used optical micromanipulation to form cell–substrate contact at controlled locations. We find that both cell-shape dynamics and cytoskeletal activity respond rapidly to the formation of cell–substrate contact.

scholarly journals Regulation of cell-substrate adhesion by proteoglycans immobilized on extracellular substrates

1989 ◽  
Vol 264 (14) ◽  
pp. 8012-8018 ◽  
Author(s):  
M Yamagata ◽  
S Suzuki ◽  
S K Akiyama ◽  
K M Yamada ◽  
K Kimata
Keyword(s):  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Substrate Adhesion

scholarly journals Single-cell transcriptomics analysis showing functional heterogeneity in decidual stromal cells during labor

2020 ◽  
pp. jim-2020-001616
Author(s):  
Jingrui Huang ◽  
Yingming Xie ◽  
Qiaozhen Peng ◽  
Weinan Wang ◽  
Chenlin Pei ◽  
...  
Keyword(s):  
Single Cell ◽  
Stromal Cells ◽  
Atp Synthesis ◽  
Sequencing Analysis ◽  
Activator Protein 1 ◽  
Oxygen Homeostasis ◽  
Substrate Adhesion ◽  
Before And After ◽  
Cell Substrate Adhesion ◽  
Labor Onset

To investigate the heterogeneity of decidual stromal cells (DSCs) and their functional alterations during delivery, we conducted single-cell RNA sequencing analysis to characterize the transcriptomic profiles of DSCs before and after labor onset. According to their transcriptomic profiles, DSCs (6382 cells) were clustered into five subgroups with different functions. Similar to stromal cells, cells in cluster 1 were involved in cell substrate adhesion. On the other hand, cells in clusters 2 and 3 were enriched in signal transduction-related genes. Labor onset led to significant alterations in many pathways, including the activator protein 1 pathway (all clusters), as well as in the response to lipopolysaccharide (clusters 1–3). The downregulated genes were involved in coagulation, ATP synthesis, and oxygen homeostasis, possibly reflecting the oxygen and energy balance during delivery. Our findings highlight that peripartum DSCs are heterogeneous and play multiple roles in labor.

scholarly journals A GTPase controls cell-substrate adhesion in Xenopus XTC fibroblasts.

1992 ◽  
Vol 118 (5) ◽  
pp. 1235-1244 ◽  
Author(s):  
M H Symons ◽  
T J Mitchison
Keyword(s):  
Control Cell ◽  
Response To Treatment ◽  
Nucleotide Analogs ◽  
Cell Contractility ◽  
Cell Rounding ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Adhesive Interactions ◽  
Cell Substrate Adhesion ◽  
Gamma S

Cell-substrate adhesion is crucial at various stages of development and for the maintenance of normal tissues. Little is known about the regulation of these adhesive interactions. To investigate the role of GTPases in the control of cell morphology and cell-substrate adhesion we have injected guanine nucleotide analogs into Xenopus XTC fibroblasts. Injection of GTP gamma S inhibited ruffling and increased spreading, suggesting an increase in adhesion. To further investigate this, we made use of GRGDSP, a peptide which inhibits binding of integrins to vitronectin and fibronectin. XTC fibroblasts injected with non-hydrolyzable analogs of GTP took much more time to round up than mock-injected cells in response to treatment with GRGDSP, while GDP beta S-injected cells rounded up in less time than controls. Injection with GTP gamma S did not inhibit cell rounding induced by trypsin however, showing that cell contractility is not significantly affected by the activation of GTPases. These data provide evidence for the existence of a GTPase which can control cell-substrate adhesion from the cytoplasm. Treatment of XTC fibroblasts with the phorbol ester 12-o-tetradecanoylphorbol-13-acetate reduced cell spreading and accelerated cell rounding in response to GRGDSP, which is essentially opposite to the effect exerted by non-hydrolyzable GTP analogs. These results suggest the existence of at least two distinct pathways controlling cell-substrate adhesion in XTC fibroblasts, one depending on a GTPase and another one involving protein kinase C.

CRISPR–Cas9 gene editing as a tool for developing immunotherapy for cancer

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Gene Editing ◽  
Genetically Engineered ◽  
Cancer Resistance ◽  
Knock Out ◽  
Tumor Tissues ◽  
Engineered T Cells ◽  
Long Time

T cells following genome editing and transformation might be detectable in peripheral blood and tumor tissues for a long time, even more than a year. The types and diversity of T-cells in peripheral blood and tumor tissues changed following transfusion of genetically modified T-cells, and some highly suspected T-cells targeting cancer cells grew, increasing the proportion of such cells. Moreover, after getting genetically engineered T cells, anticancer cytokine secretion increased. T cells changed by gene editing have certain functions, at least from an immunological standpoint. The first clinical research using the CRISPR–Cas9 gene editing method for cancer resistance is more complicated: Using CRISPR–Cas9 gene editing technology to concurrently knock out, amplify, activate and reinfuse three genes in human immune cells. This therapeutic strategy is more demanding, because the changed immune cells have a wider target scope. The data suggest that the efficacy of gene editing in immune cells was 15–45%, and the modified cells could survive long in the peripheral blood and tumor tissues of patients. After three or four months, some T-cells became central T-cells. These encouraging findings pave the way for future experimental cancer research utilizing CRISPR technology.

scholarly journals Identification of a new protein localized at sites of cell-substrate adhesion.

1986 ◽  
Vol 103 (5) ◽  
pp. 1679-1687 ◽  
Author(s):  
M C Beckerle
Keyword(s):  
Immunoblot Analysis ◽  
Rabbit Serum ◽  
Major Protein ◽  
Dynamic Interactions ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Filament Bundles ◽  
Cell Substrate Adhesion ◽  
Adhesion Plaque ◽  
New Protein

A new protein found at sites of cell-substrate adhesion has been identified by analysis of a nonimmune rabbit serum. By indirect immunofluorescence this serum stains focal contacts (adhesion plaques) and the associated termini of actin filament bundles in cultured chicken cells. Western immunoblot analysis of total chick embryo fibroblast protein demonstrated an 82-kD polypeptide to be the major protein recognized by the unfractionated serum. This 82-kD protein is immunologically distinct from other known adhesion plaque proteins such as vinculin, talin, alpha-actinin, and fimbrin. Antibody affinity-purified against the electrophoretically isolated, nitrocellulose-bound 82-kD protein retained the ability to stain the area of the adhesion plaque, which confirms that the 82-kD protein is indeed a constituent of the focal contact. The 82-kD polypeptide has a basic isoelectric point relative to actin and fibronectin, and it appears to be very low in abundance. The 82-kD protein is ubiquitous in chicken embryo tissues. However, it appears to be more abundant in fibroblasts and smooth muscle than in brain or liver. Intermediate levels of the protein were detected in skeletal and cardiac muscle. The subcellular distribution of the 82-kD protein raises the possibility that this polypeptide is involved in linking actin filaments to the plasma membrane at sites of substrate attachment or regulating these dynamic interactions.

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