Abstract
The role of membrane fluidity in determining red blood cell (RBC) deformability has been suggested by a number of studies. The present investigation evaluated alterations of RBC membrane fluidity, deformability and stability in the presence of four linear alcohols (methanol, ethanol, propanol and butanol) using ektacytometry and electron paramagnetic resonance (EPR) spectroscopy. All alcohols had a biphasic effect on deformability such that it increased then decreased with increasing concentration; the critical concentration for reversal was an inverse function of molecular size. EPR results showed biphasic changes of near-surface fluidity (i.e., increase then decrease) and a decreased fluidity of the lipid core; rank order of effectiveness was butanol > propanol > ethanol > methanol, with a significant correlation between near-surface fluidity and deformability (r = 0.697; p<0.01). The presence of alcohol enhanced the impairment of RBC deformability caused by subjecting cells to 100 Pa shear stress for 300 s, with significant differences from control being observed at higher concentrations of all four alcohols. The level of hemolysis was dependent on molecular size and concentration, whereas echinocytic shape transformation (i.e., biconcave disc to crenated morphology) was observed only for ethanol and propanol. These results are in accordance with available data obtained on model membranes. They document the presence of mechanical links between RBC deformability and near-surface membrane fluidity, chain length-dependence of the ability of alcohols to alter RBC mechanical behavior, and the biphasic response of RBC deformability and near-surface membrane fluidity to increasing alcohol concentrations.
Highlights
The physicochemical properties of membranes are of critical importance for many fundamental functions of cells, with the specific effects of these properties determined by complex cellular mechanisms [1]
Decreased deformability and decreased stability of red blood cells (RBC) might result in: (i) impaired blood flow, which may lead to ischemia and hypertension; (ii) endothelial dysfunction; (iii) chronic hypercoagulable state, which may lead to thromboembolic events [5,6,7]
EI measured at SS in the low to mid-range (i.e., 0.3–9 Pa) increased with alcohol concentration, reaching a maximum at a specific concentration that depended on the molecular size of the alcohol
Summary
The physicochemical properties of membranes are of critical importance for many fundamental functions of cells, with the specific effects of these properties determined by complex cellular mechanisms [1]. RBC have unique mechanical properties, which are crucial for the maintenance of in vivo blood flow [2]: when exposed to physiological levels of shear stress (SS), RBC are able to deform and change their shape. This ability to respond to SS, known as cellular deformability, enables these ~8 micron-diameter cells to pass through vessels with diameter as small as 3 microns, thereby significantly contributing to normal blood flow resistance at the microcirculatory level [3]. Decreased deformability and decreased stability of RBC might result in: (i) impaired blood flow, which may lead to ischemia and hypertension; (ii) endothelial dysfunction; (iii) chronic hypercoagulable state, which may lead to thromboembolic events [5,6,7]
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