Rouleaux formation: polymer induced Red Blood Cells aggregates

Plasma proteins such as fibrinogen induce the aggregation of red blood cells (RBC) into rouleaux, which are responsible for the pronounced shear thinning of blood, control the erythrocyte sedimentation rate (ESR) – a common hematological test – and are involved in many situations of physiological relevance such as structuration of blood in the microcirculation or clot formation in pathological situations. Confocal microscopy is used to characterize the shape of RBCs within rouleaux at equilibrium as a function of macromolecular concentration, revealing the diversity of contact zone morphology. Three different configurations that have only been partly predicted before are identified, namely parachute, male-female and sigmoid shapes, and quantitatively recovered by numerical simulations. Stable polymer induced clusters in capillary flow are also observed in-vivo in a mouse model by use of in intravital epiillumination microscopy and in-vitro in a microfluidic device, wherein the protein or the macromolecule concentration can be freely varied. The interaction energies between the cells are determined by use of single cell force spectroscopy and optical tweezers. Numerical simulations of flowing cells show again a good agreement with the experimental observations.