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Propriétés biophysiques des cardiomyocytes vivants en condition physio/physiopathologique et architecture des récepteurs couplés aux protéines G explorées par microscopie à force atomique

Véronique Lachaize 1
1 LAAS-ELIA - Équipe Ingénierie pour les sciences du vivant
LAAS - Laboratoire d'analyse et d'architecture des systèmes
Abstract : Heart failure is a public health problem with 1 million patients this year in France. This pathology is defined inability to heart pump sufficiently to maintain blood flow to meet the body's needs. This decrease is explicated by the loss of contractile function of the heart, caused by the necrosis of the contractile cells: cardiomyocytes. In this study, I was able to study the topographic and biomechanical modification of the cardiomyocyte membrane upstream of its rupture during necrosis, by technology derived from nanosciences : atomic force microscopy (AFM). My work reveals a highly structured membrane in healthy cardiomyocytes and a loss of this architecture in an early stage of the heart failure installation. In a second study I was interested in the oligomeric organization of a transmembrane receptors family , G protein-coupled receptors. These proteins are a privileged target for the pharmacological treatments on heart failure such as beta- Blockers and vasodilators. This oligomerization mechanism could be the key to the side effects associated with treatments. In order to study the oligomeric conformation, I used single molecule force spectroscopy and I reveal different oligomeric populations of these receptors on the membrane. The results showed a oligomeric populations distribution according the conditions (plasmid density coding for receptors / stimulation with synthetic or natural agonist). It is possible that there is a regulation of the signaling pathways, using the oligomerization for specific activation receptors. The possible difference in activity of each oligomeric population (monomer / dimer / tetramer / hexamer) appears to be a plausible explanation for the side effects of pharmacological agents. My thesis work allowed the discovery of a new track by an innovative technology, atomic force microscopy, in the treatment of heart failure.
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  • HAL Id : tel-01416906, version 2

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Véronique Lachaize. Propriétés biophysiques des cardiomyocytes vivants en condition physio/physiopathologique et architecture des récepteurs couplés aux protéines G explorées par microscopie à force atomique. Chimie thérapeutique. Université Paul Sabatier - Toulouse III, 2016. Français. ⟨NNT : 2016TOU30298⟩. ⟨tel-01416906v2⟩

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