5 years ago

Prospects for Human Erythrocyte Skeleton-Bilayer Dissociation during Splenic Flow

Prospects for Human Erythrocyte Skeleton-Bilayer Dissociation during Splenic Flow
Robert J. Asaro, Sara Salehyar, Qiang Zhu, Pedro Cabrales


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.

Publisher URL: http://www.cell.com/biophysj/fulltext/S0006-3495(17)30631-8

DOI: 10.1016/j.bpj.2017.05.052

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