Non-adsorbing macromolecules in plasma induce erythrocyte adhesion to the endothelium

Red blood cell (RBC) adhesion to the endothelium is usually insignificant. However, an enhanced adhesion can be observed in various pathological conditions such as diabetes mellitus or sickle cell disease, which is often accompanied by elevated levels of pro-adhesive plasma proteins such as fibrinogen. In the past, these proteins have only been considered to act as ligands, cross-linking the corresponding receptors on adjacent cells, but the detailed underlying mechanism often remained obscure. This work demonstrates that the presence of non-adsorbing polymers in plasma can also enhance the adhesion efficiency of RBCs to endothelial cells (ECs) through depletion interaction. Furthermore, adhesion of RBCs to ECs may be likewise promoted by the protein fibrinogen through depletion interaction. We propose an alternative mechanism for the pro-adhesive effects of plasma proteins and indicate that depletion interaction might play a significant role for the stabilization and destabilization of blood flow in health and disease.