Prospects of vesiculation occurring during splenic flow of erythrocytes are addressed via model simulations of RBC flow through the venous slits of the human spleen. Our model is multiscale and contains a thermally activated rate-dependent description of the entropic elasticity of the RBC spectrin cytoskeleton, including domain unfolding/refolding. Our model also includes detail of the skeleton attachment to the fluidlike lipid bilayer membrane, including a specific accounting for the expansion/contraction of the skeleton that may occur via anchor protein diffusive motion, that is, band 3 and glycophorin, through the membrane. This ability allows us to follow the change in anchor density and thereby the strength of the skeleton/membrane attachment. We define a negative pressure between the skeleton/membrane connection that promotes separation; critical levels for this are estimated using published data on the work of adhesion of this connection. By following the maximum range of negative pressure, along with the observed slight decrease in skeletal density, we conclude that there must be biochemical influences that probably include binding of degraded hemoglobin, among other things, that significantly reduce effective attachment density. These findings are consistent with reported trends in vesiculation that are believed to occur in cases of various hereditary anemias and during blood storage. Our findings also suggest pathways for further study of erythrocyte vesiculation that point to the criticality of understanding the biochemical phenomena involved with cytoskeleton/membrane attachment.

To understand the deformation and internal stress of a red blood cell when it is pushed through a slit by an incoming flow, we conduct a numerical investigation by combining a fluid-cell interaction model based on boundary-integral equations with a multiscale structural model of the cell membrane that takes into account the detailed molecular architecture of this biological system. Our results confirm the existence of cell 'infolding', during which part of the membrane is inwardly bent to form a concave region. The time histories and distributions of area deformation, shear deformation, and contact pressure during and after the translocation are examined. Most interestingly, it is found that in the recovery phase after the translocation significant dissociation pressure may develop between the cytoskeleton and the lipid bilayer. The magnitude of this pressure is closely related to the locations of the dimple elements during the transit. Large dissociation pressure in certain cases suggests the possibility of mechanically induced structural remodeling and structural damage such as vesiculation. With quantitative knowledge about the stability of intra-protein, inter-protein and protein-to-lipid linkages under dynamic loads, it will be possible to achieve numerical prediction of these processes.

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