Red blood cell adhesion can be reduced by non-reactive macromolecules

To date, the mechanisms behind red blood cell (RBC) adhesion remain unclear. However, polymer depletion at the red cell surface has been shown to play a significant role. Interestingly, most previous studies have focused on the adhesion-promoting effects of one type of large polymer or plasma protein. However, the situation in vivo is more complex in that one needs to consider a mixture of various bio-macromolecules. To explore this complexity, Interference Reflection Microscopy was used to investigate how mixtures of various polymers affect RBC adhesion. RBC adhesion to albumin-coated glass coverslips was studied in the presence of two pro-adhesion polymers [dextran70 kDa and 35 kDa poly(ethylene glycol) (PEG 35)] with and without three types of smaller polymers: dextran 10 kDa, PEG 10 kDa and Poloxamer 188. Our findings show that the presence of small polymers can inhibit the adhesion-promoting effects of dextran 70 and PEG 35, with a more pronounced reduction for heterogeneous mixtures. Interpretation of our results in terms of the depletion model appears appropriate, in that our findings are consistent with the assumption that this reduction occurs because of an increase of small molecules in the depletion region. This study thus suggests that depletion interaction can control cell-cell interactions in complex environments (e.g., in vivo), and indicates that considering the interplay of all plasma constituents is important in order to understand the pathophysiology of diseases associated with cell adhesion and vascular complications.