A5043009093- Cell Adhesion Molecules Research
- Collagen: Extraction and Characterization
- Platelet Disorders and Treatments
- Antiplatelet Therapy and Cardiovascular Diseases
- Infective Endocarditis Diagnosis and Management
- Blood Coagulation and Thrombosis Mechanisms
- Protease and Inhibitor Mechanisms
- Streptococcal Infections and Treatments
- Bone Tissue Engineering Materials
- Osteoarthritis Treatment and Mechanisms
- Chemical Synthesis and Analysis
- Synthesis and pharmacology of benzodiazepine derivatives
- Otolaryngology and Infectious Diseases
- Synthesis and Reactivity of Heterocycles
- Click Chemistry and Applications
- Cellular Mechanics and Interactions
- Electrospun Nanofibers in Biomedical Applications
- Oral microbiology and periodontitis research
- Supramolecular Self-Assembly in Materials
- Chemical synthesis and pharmacological studies
- Ion Channels and Receptors
- Angiogenesis and VEGF in Cancer
- Complement system in diseases
- Venous Thromboembolism Diagnosis and Management
- Schizophrenia research and treatment
Université Claude Bernard Lyon 1
2022-2025
Centre National de la Recherche Scientifique
2012-2025
University of Cambridge
2015-2025
Biologie Tissulaire et Ingénierie Thérapeutique
2022
Institut des Biomolécules Max Mousseron
2012-2014
École Nationale Supérieure de Chimie de Montpellier
2014
Université de Montpellier
2014
Essentials•Glycoprotein VI (GPVI) binds collagen, starting thrombogenesis, and fibrin, stabilizing thrombi.•GPVI‐dimers, not monomers, recognize immobilized fibrinogen fibrin through their D‐domains.•Collagen, D‐fragment D‐dimer may share a common or proximate binding site(s) on GPVI‐dimer.•GPVI‐dimer–fibrin interaction supports spreading, activation adhesion involving αIIbβ3.Summary: BackgroundPlatelet collagen receptor Glycoprotein initiating stabilizes thrombi by fibrin.ObjectivesTo...
Drug delivery to the central nervous system is hindered by presence of physiological barriers such as blood-brain barrier. To accomplish task nutrient transport, brain endothelium endowed with various transport systems, including receptor-mediated transcytosis (RMT). This can be used shuttle therapeutics into (CNS) in a noninvasive manner. Therefore, low-density lipoprotein receptor (LDLR) relevant target for delivering drugs. From an initial phage display biopanning, series peptide ligands...
Abstract Platelets protect the vascular system during damage or inflammation, but platelet activation can result in pathological thrombosis. Activated platelets release a variety of extracellular vesicles (EVs). EVs shed from plasma membrane often expose phosphatidylserine (PS). These are pro-thrombotic and increased number many cardiovascular metabolic diseases. The mechanisms by which PS-exposing activated not well characterised. Cholesterol-rich lipid rafts provide platform for...
Ibrutinib and acalabrutinib are irreversible inhibitors of Bruton tyrosine kinase used in the treatment B-cell malignancies. They bind irreversibly to cysteine 481 kinase, blocking autophosphorylation on 223 phosphorylation downstream substrates including phospholipase C-γ2. In present study, we demonstrate that concentrations ibrutinib block activity, as shown by loss at C-γ2, delay but do not aggregation response a maximally-effective concentration collagen-related peptide or collagen....
Abstract Procoagulant platelets promote thrombin generation during thrombosis. Platelets become procoagulant in an all-or-nothing manner. We investigated how distinct Ca2+ signaling between platelet subpopulations commits some to procoagulant, using the high-affinity indicator Fluo-4, which may saturated stimulation, or low-affinity Fluo-5N, reports only very high cytosolic concentrations. All activated had Fluo-4 fluorescence. However, Fluo-5N–loaded platelets, fluorescence, indicating...
Exogenous zinc induces full aggregation of washed platelet suspensions. Zinc-induced is biphasic, suggestive secondary signalling-mediated activation.
Collagen is frequently advocated as a scaffold for use in regenerative medicine. Increasing the mechanical stability of collagen widely achieved by cross-linking using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). However, this treatment consumes carboxylate-containing amino acid sidechains that are crucial recognition cell-surface integrins, abolishing cell adhesion. Here, we restore reactivity to cross-linked type I film covalently linking synthetic...
Objectives Platelet activation underpins thrombus formation in ischemic stroke. The active, dimeric form of platelet receptor glycoprotein (GP) VI plays key roles by binding ligands collagen and fibrin, leading to activation. We investigated whether patients presenting with stroke expressed more GPVI on their surface had active circulating platelets as measured P-selectin exposure. Methods 129 or hemorrhagic were recruited within 8h symptom onset. Whole blood was analyzed for...
The M protein is an essential virulence factor of Streptococcus pyogenes , or group A streptococci (GAS), one the most common and dangerous human pathogens. Molecular functional characterization variants their interactions with host components crucial for understanding streptococcal pathogenesis vaccine development. M3 produced by prevalent emm 3 GAS serotype, which frequently associated severe invasive diseases. Here we characterize interaction collagens through detailed structural...
The M protein is an essential virulence factor of Streptococcus pyogenes , or group A streptococci (GAS), one the most common and dangerous human pathogens. Molecular functional characterization variants their interactions with host components crucial for understanding streptococcal pathogenesis vaccine development. M3 produced by prevalent emm 3 GAS serotype, which frequently associated severe invasive diseases. Here we characterize interaction collagens through detailed structural...
Accurate evaluation of the biological performance biomaterials requires correct assessment their native-like cell ligation properties. However, attachment studies often overlook details substrate-cell binding mechanisms, be they integrin-mediated or non-specific, and ignore class- species-specificities adhesion receptor involved. In this work we have used different collagen (Col) substrates (fibrillar collagens I, II III network-forming Col IV), containing affinity cell-recognition motifs,...
Neonatal platelets are hypo-reactive to the tyrosine kinase-linked receptor agonist collagen. Here, we have investigated whether hypo-responsiveness is related altered levels of glycoprotein VI (GPVI) and integrin α2β1, or defects in downstream signalling events by comparison platelet activation C-type lectin-like 2 (CLEC-2). GPVI CLEC-2 activate a Src- Syk-dependent pathway upstream phospholipase C (PLC) γ2. Phosphorylation conserved YxxL sequence known as (hemi)...
Active targeting and delivery to pathophysiological organs of interest is paramount importance increase specific accumulation therapeutic drugs or imaging agents while avoiding systemic side effects. We recently developed a family new peptide ligands the human rodent LDL receptor (LDLR), an attractive cell-surface with high uptake activity local enrichment in several normal pathological tissues (Malcor et al., J. Med. Chem. 2012, 55 (5), 2227). Initial chemical optimization 15-mer, all...
Abstract Collagen triple helix folds in two steps: nucleation of three polypeptides at the C-termini followed by zip-chain like propagation. The helices found all domains life as well viruses contain upto 6000 amino acids each polypeptide that are also frequently interrupted with non-helical sequences disrupt folding and reduce stability. Given length disruptive interruptions, compensating mechanisms stabilize against local unfolding during propagation offset entropic cost long not fully...
The collagen-binding integrins recognise collagen through their inserted (I) domain, where co-ordination of a Mg2+ ion in the metal ion-dependent site is reorganised by ligation glutamate residue found specific hexapeptide motifs. Here we show that GROGER, N-terminal domain collagens I and III, only weakly recognised α10β1, an important receptor on chondrocytes, contrasting with other integrins. Alignment sequence molecular modelling revealed clash between unique arginine (R215) α10β1...
Abstract Citalopram prevents serotonin (5-HT) uptake into platelets by blocking the reuptake transporter (SERT). Although some clinical data suggest that selective inhibitors (SSRIs) may affect haemostasis and thrombosis, these poorly-characterised effects are not well understood mechanistically useful in vitro is limited. We sought to determine whether inhibitory of citalopram on mediated via its pharmacological inhibition 5-HT transport. quantified potency ( RS )-, R )- S )-citalopram...
Collagen-based scaffolds may require chemical crosslinking to achieve mechanical properties suitable for tissue engineering. Carbodiimide treatment, often used this purpose, consumes amino acid side chains required receptor recognition, thus reducing cell–collagen interaction. Here, we restore recognition and function of both von Willebrand Factor (VWF) Discoidin Domain Receptor 2 (DDR2) crosslinked collagen films by derivatisation with a specific triple-helical peptide (THP), an approach...
Abstract Porous biomaterials which provide a structural and biological support for cells have immense potential in tissue engineering cell-based therapies repair. Collagen that can host endothelial represent promising tools the vascularization of engineered tissues. Three-dimensional collagen scaffolds possessing controlled architecture mechanical stiffness are obtained through freeze–drying suspensions, followed by chemical cross-linking maintains their stability. However, renders activity...
Integrins are a family of 24 adhesion receptors which both widely-expressed and important in many pathophysiological cellular processes, from embryonic development to cancer metastasis. Hence, integrin inhibitors valuable research tools may have promising therapeutic uses. Here, we focus on the four collagen-binding integrins α1β1, α2β1, α10β1 α11β1. TC-I-15 is small molecule inhibitor α2β1 that inhibits platelet collagen thrombus deposition, obtustatin an α1β1-specific disintegrin...
In this study, we investigated the role of cardiomyocyte (CM) and endothelial cell (EC) specific interactions with collagen in assembly an operational myocardium vitro. Engineered cardiac patches represent valuable tools for myocardial repair following infarction are generally constituted a suitable biomaterial populated by CMs supportive types. Among those, ECs required tissue vascularization positively modulate CM function. To direct function human embryonic stem (hESC)-derived EC seeded...