Focal adhesion stabilization by enhanced integrin-cRGD binding affinity

2017 ◽  
Vol 18 (1-2) ◽  
Author(s):  
Diego Pallarola ◽  
Ilia Platzman ◽  
Alexander Bochen ◽  
Elisabetta A. Cavalcanti-Adam ◽  
Markus Axmann ◽  
...  

AbstractIn this study we investigate the impact of ligand presentation by various molecular spacers on integrin-based focal adhesion formation. Gold nanoparticles (AuNPs) arranged in hexagonal patterns were biofunctionalized with the same ligand head group, cyclic Arg-Gly-Asp [

2012 ◽  
Vol 287 (33) ◽  
pp. 27499-27509 ◽  
Author(s):  
Tae Kyoung Kwak ◽  
Mi-Sook Lee ◽  
Jihye Ryu ◽  
Yoon-Ju Choi ◽  
Minkyung Kang ◽  
...  

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Xiaoqian Fang ◽  
Dong H Kim ◽  
Teresa Santiago-Sim

Introduction: An intracranial aneurysm (IA) is a weak spot in cerebral blood vessel wall that can lead to its abnormal bulging. Previously, we reported that mutations in THSD1 , encoding thrombospondin type-1 domain-containing protein 1, are associated with IA in a subset of patients. THSD1 is a transmembrane molecule with a thrombospondin type-1 repeat (TSR). Proteins with TSR domain have been implicated in a variety of processes including regulation of matrix organization, cell adhesion and migration. We have shown that in mouse brain Thsd1 is expressed in endothelial cells. Hypothesis: THSD1 plays an important role in maintaining the integrity of the endothelium by promoting adhesion of endothelial cells to the underlying basement membrane. Methods: Human umbilical vein endothelial cells are used to investigate the role of THSD1 in vitro . THSD1 expression was knocked-down by RNA interference. Cell adhesion assay was done on collagen I-coated plates and focal adhesion formation was visualized using immunofluorescence by paxillin and phosphorylated focal adhesion kinase (pFAK) staining. THSD1 re-expression is accomplished by transfection with a pCR3.1-THSD1-encoding plasmid. Results: Knockdown of THSD1 caused striking change in cell morphology and size. Compared to control siRNA-treated cells that exhibited typical cobblestone morphology, THSD1 knockdown cells were narrow and elongated, and were significantly smaller ( p <0.01). Cell adherence to collagen I-coated plates was also attenuated in THSD1 knockdown cells ( p <0.01). Consistent with this finding is the observation that the number and size of focal adhesions, based on paxillin and pFAK staining, were significantly reduced after THSD1 knockdown ( p <0.01). These defects in cell adhesion and focal adhesion formation were rescued by re-expression of wild type THSD1 ( p <0.05). In contrast, initial studies indicate that expression of mutated versions of THSD1 as seen in human patients (L5F, R450*, E466G, P639L) could not restore cell adhesion and focal adhesion formation to wild type levels. Conclusions: Our studies provide evidence for a role of THSD1 and THSD1 mutations in endothelial cell adhesion and suggest a possible mechanism underlying THSD1 -mediated aneurysm disease.


2020 ◽  
Vol 12 (13) ◽  
pp. 14924-14932
Author(s):  
Dainelys Guadarrama Bello ◽  
Aurélien Fouillen ◽  
Antonella Badia ◽  
Antonio Nanci

2018 ◽  
Vol 114 (3) ◽  
pp. 516a
Author(s):  
Tejeshwar C. Rao ◽  
Tara M. Urner ◽  
Victor Pui-Yan Ma ◽  
Khalid Salaita ◽  
Alexa L. Mattheyses

Author(s):  
Aleksandra Makowiecka ◽  
Natalia Malek ◽  
Ewa Mazurkiewicz ◽  
Ewa Mrówczyńska ◽  
Dorota Nowak ◽  
...  

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