Vinculin

Calcium (Ca2 + ) homeostasis is essential in conducting various cellular processes including nerve transmission, muscular movement, and immune response. Changes in Ca2 +  concentration in the cytoplasm are significant in bringing about various immune responses such as pathogen clearance and apoptosis. Various key players are involved in calcium homeostasis such as calcium binders, pumps, and channels. Sequence-based evolutionary information has recently been exploited to predict the biophysical behaviors of proteins, giving critical clues about their functionality...

The mechanistic basis for the metastasis of Ewing sarcomas remains poorly understood, as these tumors harbor few mutations beyond the chromosomal translocation that initiates the disease. Instead, the epigenome of Ewing sarcoma (EWS) cells reflects the regulatory state of genes associated with the DNA binding activity of the fusion oncoproteins EWSR1::FLI1 or EWSR1::ERG. In this study, we examined the EWSR1::FLI1/ERG's repression of transcription factor genes, concentrating on those that exhibit a broader range of expression in tumors than in EWS cell lines...

SLK controls the cytoskeleton, cell adhesion, and migration. Podocyte-specific deletion of SLK in mice leads to podocyte injury as mice age and exacerbates injury in experimental focal segment glomerulosclerosis (FSGS; adriamycin nephrosis). We hypothesized that adhesion proteins may be substrates of SLK. In adriamycin nephrosis, podocyte ultrastructural injury was exaggerated by SLK deletion. Analysis of a protein kinase phosphorylation site dataset showed that podocyte adhesion proteins-paxillin, vinculin, and talin-1 may be potential SLK substrates...

Axon regeneration requires actomyosin interaction, which generates contractile force and pulls the regenerating axon forward. In Caenorhabditis elegans, TLN-1/talin promotes axon regeneration through multiple down-stream events. One is the activation of the PAT-3/integrin-RHO-1/RhoA GTPase-LET-502/ROCK (Rho-associated coiled-coil kinase)-regulatory non-muscle myosin light-chain (MLC) phosphorylation signaling pathway, which is dependent on the MLC scaffolding protein ALP-1/ALP-Enigma. The other is mediated by the F-actin-binding protein DEB-1/vinculin and is independent of the MLC phosphorylation pathway...

Transforming growth factor (TGF)-β1 is a multifunctional cytokine that plays important roles in health and disease. Previous studies have revealed that TGFβ1 activation, signaling, and downstream cell responses including epithelial-mesenchymal transition (EMT) and apoptosis are regulated by the elasticity or stiffness of the extracellular matrix. However, tissues within the body are not purely elastic, rather they are viscoelastic. How matrix viscoelasticity impacts cell fate decisions downstream of TGFβ1 remains unknown...

Collagen with its bioactive ligand motives would be predestined as coating on bone implant surfaces like titanium hip stems to facilitate receptor-mediated cell adhesion and thereby improve early osseointegration. Unfortunately, collagen as coating exhibits very low proteolytic resistance in vivo. To overcome this limitation, different crosslinking methods of collagen (transglutaminase, GTA, EDC/NHS, riboflavin, and lysyl oxidase) with silanized titanium alloy (Ti6Al4V) were investigated in terms of degradation resistance, hydrolysis stability, tensile strength, and metabolic cell activity...

Mechanical cues in the tumor microenvironment interplay with internal cellular processes to control cancer cell migration. Microscale pores present in tumor tissue confer varying degrees of confinement on migrating cells, increasing matrix contact and inducing cytoskeletal rearrangement. Previously, we observed that increased collagen matrix contact significantly increased cell migration speed and cell-induced strains within the matrix. However, the effects of this confinement on future cell migration are not fully understood...

Osteointegration is a key process during dental implant placement and is related to titanium surface topography. Implant coating and surface modification methods ameliorate the bone production and the osteogenic process. The current work aimed at evaluating the biological outcomes of two different surfaces of dental implants, machined and titanium nitride (TiN) coated, at an inflammation level using an in vitro model of human periodontal ligament stem cells. The TLR4/MyD88/NF-κB p65/NLRP3 pathway induced by the Porphyromonas gingivalis lipopolysaccharide was studied by means of gene- and protein-level expression...

Diarrhea-predominant irritable bowel syndrome (IBS-D), associated with increased intestinal permeability, inflammation, and small intestinal bacterial overgrowth, can be triggered by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by gastroenteritis-causing pathogens and may underlie IBS-D development, through molecular mimicry with vinculin. Here, we examine the effects of exposure to CdtB alone on gut microbiome composition, host intestinal gene expression, and IBS-D-like phenotypes in a rat model...

The ability of cells and tissues to respond differentially to mechanical forces applied in distinct directions is mediated by the ability of load-bearing proteins to preferentially maintain physical linkages in certain directions. However, the molecular basis and biological consequences of directional force-sensitive binding remain unclear. Vinculin (Vcn) is a load-bearing linker protein that exhibits directional catch bonding due to interactions between the Vcn tail domain (Vt) and filamentous (F)-actin. We developed a computational approach to predict Vcn residues involved in directional catch bonding and produced a set of associated Vcn variants with unaltered Vt structure, actin binding, or phospholipid interactions...

Bone resident cells are constantly subjected to a range of distinct mechanical loadings, which generates a complex microenvironment. In particular, hydrostatic pressure (HP) has a key impact on modulation of cell function and fate determination. Although HP is a constant mechanical stimulus, its role in regulating the osteogenesis process within a defined 3D microenvironment has not been comprehensively elucidated. Perceiving how environmental factors regulate the differentiation of stem cells is essential for expanding their regenerative potential...

The ability of cells to move in a mechanically coupled, coordinated manner, referred to as collective cell migration, is central to many developmental, physiological, and pathophysiological processes. Limited understanding of how mechanical forces and biochemical regulation interact to affect coupling has been a major obstacle to unravelling the underlying mechanisms. Focusing on the linker protein vinculin, we use a suite of Förster resonance energy transfer-based biosensors to probe its mechanical functions and biochemical regulation, revealing a switch that toggles vinculin between loadable and unloadable states...

OBJECTIVES: This in vitro study aimed to evaluate the cell viability and expression of proteins related to angiogenesis, adhesion, and cell survival (vascular endothelial growth factor, paxillin, vinculin, fibronectin, and protein kinase B) in gingival fibroblasts that were cultured on titanium discs treated with or without nanohydroxyapatite and exposed to platelet-rich fibrin (PRF)-conditioned medium. METHODS: To obtain the conditioned medium, the PRF membranes were prepared and incubated for 48 h in a culture medium without fetal bovine serum...

Recombinant humanized collagen (rhCol) was an extracellular matrix (ECM)-inspired biomimetic biomaterial prepared by biosynthesis technology, which was considered non-allergenic and could possibly activate tissue regeneration. The influence of tag sequence on both structures and performances of rhCol type III (rhCol III) was investigated, and the effect of rhCol III on cell behaviors was evaluated and discussed using Schwann cells (SCs) as in vitro model that was critical in the repair process after peripheral nerve injury...

Promoting osseointegration is an essential step in improving implant success rates. Lithium has gradually gained popularity for promoting alkaline phosphatase activity and osteogenic gene expression in osteoblasts. The incorporation of lithium into a titanium surface has been reported to change its surface charge, thereby enhancing its biocompatibility. In this study, we applied anodization as a novel approach to immobilizing Li on a titanium surface and evaluated the changes in its surface characteristics...

In-depth understanding of the mechanisms underlying the adhesion of myocardial cells holds significant importance for the development of effective therapeutic biomaterials aimed at repairing damaged or pathological myocardial tissues. Herein, we present evidence that myocardial cells (H9C2) exhibit integrin-based mechanosensing during the initial stage of adhesion (within the first 2 h), enabling them to recognize and respond to variations in substrate stiffnesses. Moreover, the bioinformatics analysis of RNA transcriptome sequencing (RNA-seq) reveals that the gene expressions associated with initial stage focal adhesion (Ctgf, Cyr61, Amotl2, Prickle1, Serpine1, Akap12, Hbegf, and Nedd9) are up-regulated on substrates with elevated Young's modulus...

Chronic wounds are challenging to heal and increase global mortality. The effectiveness of skin graft is limited by rejection, fibrosis, and inadequate donor site. Multifunctionalised-hydrogel skin substitutes promoted higher wound healing by maintaining the moisture microenvironment and permit gas exchange/nourishment in prolong cell viability/activity. The purpose of this study was to evaluate a skin substitute using two strategies; via injectable and 3D bioprinting technique. New hydrogel formulations that composed of gelatin (GE) and polyvinyl-alcohol (PVA) were constructed using a pre-mix crosslinking approach with genipin (GNP) to generate the biodegradable and biocompatible skin substitute with reduced secondary traumatic wound...

Immune cells are highly dynamic and able to migrate through environments with diverse biochemical and mechanical composition. Their migration has classically been defined as amoeboid under the assumption that it is integrin-independent. Here we show that activated primary Th1 T cells require both confinement and extracellular matrix protein to migrate efficiently. This migration is mediated through small and dynamic focal adhesions that are composed of the same proteins associated with canonical mesenchymal focal adhesions, such as integrins, talin, and vinculin...

BACKGROUND: Integrins are closely related to mechanical conduction and play a crucial role in the osteogenesis of human mesenchymal stem cells. Here we wondered whether tensile stress could influence cell differentiation through integrin αVβ3. METHODS: We inhibited the function of integrin αVβ3 of human mesenchymal stem cells by treating with c(RGDyk). Using cytochalasin D and verteporfin to inhibit polymerization of microfilament and function of nuclear Yes-associated protein (YAP), respectively...

Vinculin is an actin-binding protein (ABP) that strengthens the connection between the actin cytoskeleton and adhesion complexes. It binds to β-catenin/N-cadherin complexes in apical adherens junctions (AJs), which maintain cell-to-cell adhesions, and to talin/integrins in the focal adhesions (FAs) that attach cells to the basal membrane. Here, we demonstrate that β-catenin targets vinculin to the apical AJs and the centrosome in the embryonic neural tube (NT). Suppression of vinculin slows down the basal-to-apical part of interkinetic nuclear migration (BAINM), arrests neural stem cells (NSCs) in the G2 phase of the cell cycle, and ultimately dismantles the apical actin cytoskeleton...