The Mechanical Properties of Erythrocytes Are Influenced by the Conformational State of Albumin

The mechanical stability and deformability of erythrocytes are vital for their function as they traverse capillaries, where shear stress can reach up to 10 Pa under physiological conditions. Human serum albumin (HSA) is known to help maintain erythrocyte stability by influencing cell shape, membrane integrity, and resistance to hemolysis. However, the precise mechanisms by which albumin exerts these effects remain debated, with some studies indicating a stabilizing role and others suggesting the opposite. This review highlights that under high shear rates, albumin molecules may undergo unfolding due to normal stress differences. Such structural changes can significantly alter albumin's interactions with the erythrocyte membrane, thereby affecting cell mechanical stability. We discuss two potential scenarios explaining how albumin influences erythrocyte mechanics under shear stress, considering both the viscoelastic properties of blood and those of the erythrocyte membrane. Based on theoretical analyses and experimental evidence from the literature, we propose that albumin's effect on erythrocyte mechanical stability depends on (i) the transition between unfolded and folded states of the protein and (ii) the impact of shear stress on the erythrocyte membrane's ζ-potential. Understanding these factors is essential for elucidating the complex relationship between albumin and erythrocyte mechanics in physiological and pathological conditions.