In vitro Characterization and Numerical Simulations of Red Blood Cell Transmigration Through Splenic Inter-Endothelial Slits

Abstract

During their circulation through the spleen, red blood cells (RBCs) are forced to squeeze through gaps between endothelial cells that are ∼8 times narrower than its diameter. The ensuing squeezing motion causes large RBC deformations that remove old and diseased cells from the circulation. There is limited data about the deformation and stress experienced by RBCs. To study the mechanics of RBC splenic filtration, we designed and characterized a family of microfluidic devices where a suspension of human RBCs flows through an array (N = 50) of channels of controlled length (L), width (W) and height (H). We varied these geometrical parameters (0.75<W<L<H2 um) RBCs reorient into the direction of less constrain, cell diameter is parallel to the height of the channel, whereas in narrower channels, cells fold into themselves (U shape) experimenting large deformations. We examined computationally the deformation and stress of these folded cell shapes under different flow rates and slit geometries. We explored the possibility of deformation-induced spectrin unfolding and dissociation, which might play an important role in pathological mechanisms of hereditary RBC membrane disorders.