Thesis defense
Title : Dynamics of red blood cells in biomimetic splenic slits
Abstract :
The blood circulation in the vascular system is a physical tour de force. Red blood cells (RBCs), the most abundant of the blood components, are responsible for distributing oxygen throughout the body. To perform this task, RBCs are known to be highly deformable, a characteristic that allows them to pass through capillaries that are thinner than their size. The RBC deformability is periodically monitored by the spleen : those that cannot pass through the inter-endothelial splenic slits are entrapped and destroyed by macrophages. This can be considered as a fitness test.
Today, the dynamics of the RBC passage through these inter-endothelial splenic slits is still poorly understood. Thus, the objective of my thesis was to study the physical mechanisms of the microcirculation of RBCs during their passage through these slits.
To do so, we developed a new on chip PDMS device containing high aspect ratio slits with sub-micrometer width, reproducing the physiological dimensions of these slits, the flow conditions, and where the RBC dynamics can be observed by videomicroscopy. By pushing them through these sub-micrometer slits, we quantitatively study retention rates, passage dynamics and deformation of RBCs as a function of physical parameters (slit dimensions, pressure differentials, temperatures) and biological parameters (mechanosensitive ion channel). We show that RBCs are able to form two spheres of equal volume connected by a thin membrane tube. We also noticed that RBCs are able to unfold their spectrin cytoskeleton. By further investigating cell morphologies during this biomimetic filtration process, we show original deformation modes with the formation of « tip » at the front of the cells. Conjointly, with our collaborator (Z. Peng, UCI, USA) we use numerical simulations that reproduce the observed RBC dynamics. The computational approach and the dimensional analysis allow us to understand the physical mechanisms of RBC splenic filtration through the slits.
The Phd committee members are :
Hèlène Guizouarn, Institut de Biologie Valrose, Nice: Reviewer
Thomas Podgorski, Laboratoire Rhéologie et Procédés, Grenoble: Reviewer
Catherine Badens, Marseille Medical Genetics, Marseille: Member
Pierre Buffet, Institut National de Transfusion Sanguine, Paris: Member
Samuel Vergès, Laboratoire Hypoxie et Physiopathologies, Grenoble: Member
Annie Viallat, CINAM: PhD co-advisor
Emmanuèle Helfer, CINAM: PhD advisor
The defense will be in french.