Experimental determination of human erythrocyte membrane permeability coefficients for a series of amides

Erythrocyte membrane permeability coefficients have been determined for a series of amides by a method based on the physical and mathematical modelling of hypotonic haemolysis process. The results show that penetration of the substances occurs by two alternative ways through aqueous pores formed by proteins and by the direct dissolving of the molecules in membrane lipids. This conclusion can be confirmed by the correlation analysis between permeability coefficients of native erythrocytes and those pre-incubated with the monosodium salt of p-chloromercuribenzenesulfonic acid (pCMBS), and the partition coefficients of the substances in hydrophilic-hydrophobic phases. Penetration of substances through hydrophilic channels is limited by the sterical factor and diameter in particular. Permeability coefficients for erythrocytes pre-incubated with pCMBS increase in an accordance with the rise of the partition coefficients with correlation coefficient of 0.94, thereby indicating a lipid route of permeation of molecules through erythrocyte membranes.     

Erythrocyte membrane permeability for a series of diols

Erythrocyte membrane permeability coefficients for a series of diols have been defined by the method developed. The method is based on the physical and mathematical modeling of hypotonic hemolysis process. There have been also determined membrane permeability coefficients for erythrocytes treated with p-chloromercuribenzenesulfonic acid monosodium salt (pCMBS), which is known to block aqueous protein channels. Permeating process is shown to be conditioned both by hydrophilic/hydrophobic properties of the molecules and their geometrical parameters. The obtained results propose that, when exceeding the molecules diameter over a value of 4 A, the permeability coefficient reduces due to decreasing of flow through the aqueous protein pores of a constant size. Permeability coefficients for comparatively hydrophobic molecules are almost directly proportional to the coefficients of partition between hydrophobic and hydrophilic phases, by pointing to a lipid way of permeation of these molecules through erythrocyte membranes.     

Estimation of erythrocyte population state by the spherical index distribution

The densities of cell distributions by spherical index (SI) in erythrocyte populations from healthy adults and donors with endocrine pathologies were determined via the developed method. The investigation shows that this characteristic varies for different donors, thereby reflecting the erythrocyte population state of an individual donor. Individual distribution curves obtained from healthy donors are close to Gaussian and are characterized by smooth curve plot with one maximum. Cells distribution by SI in donors with endocrine pathologies has a polymodal character. Our research shows that the developed method for determining erythrocyte distribution density by SI is a sensitive and informative test for quantitative evaluation of an erythrocyte population state. Moreover, this characteristic has clear physical and physiological significance, because an erythrocyte shape is strongly conditioned by the cell age and influences the ability to pass through microcapillaries in blood circulation.     

Permeability of rat and rabbit erythrocyte membranes for a series of amides

Permeability coefficients of rat and rabbit erythrocyte membranes for a series of amides, as well as for erythrocytes treated with p-chloromercuribenzenesulfonic acid monosodium salt (pCMBS) have been determined at 25 and 37 degrees C. Directly proportional dependence of the pCMBS treated erythrocyte permeability for investigated substances and their partition coefficients between the hydrophobic phase and water as well as the values of activation energy of this process indicate that penetration of small hydrophilic molecules is realized by passive diffusion through the lipid bilayer. The results obtained indicate that penetration of small hydrophilic molecules of formamide through lipids is determined by the existence of a free space between hydrocarbon chains that arises from kink formation. The differences in permeability between rat and rabbit erythrocyte membranes could arise in particular as a result of the differences in lipid composition.