Starting in January 2015 

Two of the most important genetic diseases of red blood cells (RBCs), namely sickle cell anemia – a very handicapping and the most prevalent generic disease in the world- and hereditary spherocytosis are both characterized by an increase in the cell rigidity The resulting lack of deformability occurs either because of the formation of rigid fibers of haemoglobin S in the cytoplasm or via changes in membrane proteins which in turn alter the cytoskeleton resulting in a spherical cell shape. These changes result in problems of circulation of RBCs in narrow capillaries and through the thin slits of splenic sinusoids- situations where the RBCs may be subject to very strong deformations. In spite of a lot of work on blood flow, the role of the deformation parameters, that is to say, the mechanical properties of RBCs that govern their behavior in micro-flow, is poorly understood.

In this project, we propose the challenge of understanding the dynamics of RBCs in the microcirculation in the context of sickle cell anemia and hereditary spherocytosis. We shall develop a combination of micro and nano techniques and in vitro approaches to study the mechanical properties of the pathological RBCs, as well as their individual and collective dynamics in biomimetic micro-flows.

The work of the postdoc will be to create controlled micro-environments and micro-flows in which the channels will be developed to mimic or induce different situations relevant to the project.
For the dynamics and mechanical properties of individual RBCs. Micro-channels with diameters ranging from 3 to 20 μm will be fabricated. The floor of the channels will be patterned with topographic structures with sizes varying from the nano- to the microscale with varying periodicities to generate constrictions of the channel and recirculation of the flow. Adequate patterning strategies will be considered for the different scales using different techniques such as ordered anodic alumina (OAA) membranes, topographic PDMS replica, lift-off, stamping, colloidal bead masks….
For the margination and segregation of RBCs in a shear flow and in confined microflows, additional disrupting large topographic obstacles will be built to create symmetry ruptures of the flow.
To study thrombus and vasooclusion in sickle cell anemia, channels will be built with constrictions and reductions of their diameter. Effects of walls adhesiveness will be studied by chemically patterning the channels with adhesion proteins (Poly-lysine, fibronectine, etc…). Also, large obstacles functionalized with adhesion proteins will be displayed inside the channels.

The postdoc will also participate to flow studies.

Postdoc competences: Nano/Micro Fabrication, Surface functionalization, PDMS, Surface patterning

Contact: Anne Charrier
charrier<στο>cinam.univ-mrs.fr