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The reversible aggregation of red blood cells (RBC) is an essentialintrinsic property of blood, which has a direct effect on blood viscosity and therefore on the circulation of blood throughout the body. Up to date there is no clear understanding of the RBC aggregation mechanism. Measurement of interaction forces between RBCin aggregates in various polymer solutions that induce or inhibit aggregation with laser tweezers allow for assessing the specific features of aggregation and better understanding the mechanism of this important process. We have studied RBC interaction in blood plasma and serum,and in the solutions of four different polymers that induce RBC aggregation: fibrinogen, albumin and γ-globulin as plasma proteins, and dextran as an example of neutral macromolecules. Measurements were performed with homemade double-channel laser tweezers (LT). Interaction forces acting in RBCaggregates were measured separately for the aggregating and disaggregating processes. Briefly the measurement process consisted of thefollowing steps: (1) two cells were manipulated with LT and the artificial aggregate was formed; (2)piconewton range forces of their interaction were measured. The measured parameters were the minimum force to separate thecells from each other, either fully or partly (disaggregating force - FD¬) andtheminimum force to hold cells from spontaneously overlapping to each other (aggregating force – FA). Measurements of FA and FDwere done for various dependenceslike on interaction area and on thetime between cells, on theconcentration of polymers and temperature. The comparison of FA and FD showed that RBC interaction dynamicsis manifested differently depending on the content of the solution. In blood plasma and serum,FDis about 2-3 times higher than FA.While FAlinearly decreasesalong with decreasing interaction area(IA) between the cells, FD in contrast increased. In dextran solution, FA equals to FD, both linearly decreasing with IA. In protein solutions, FAis nullas the cells do not overlap to each other spontaneously, however,the cells interact strongly within the IA formed with LT.Meanwhile FD– exhibit the same dependence as in blood plasma. The concentration dependence is clearly observed for all types of macromolecules. As for albumin, it does not induce any interaction between the cells itself but enhancesthe interaction if any other proteins is present, thus showing a synergetic effect of polymers. Based on our measurement results the interaction energies between RBC are calculated, and the interaction mechanics are speculated. These results seem to support the “cross-bridge” model enhanced with the supposition about the migration of cross-bridges to describe RBC interaction in plasma and protein solutions. Yet further investigation is required to fully assess the mechanism of RBC aggregation.