Acceleration of phospholipid flip-flop in the erythrocyte membrane by detergents differing in polar head group and alkyl chain length

The detergents, alkyltrimethylammonium bromide, N-allcyl-N,N-dimethyl-3-amm onio-1-propanesulfonate (zwittergent), alkane sulfonate, alkylsulfate, alky l-beta -D-glucopyranoside, alkyl-beta -D-maltoside, dodecanoyl-N-methylgluc amide, polyethylene glycol monoalkyl ether and Triton X-100, all produce a concentration-dependent acceleration of the slow passive transbilayer movem ent of NBD-labeled phosphatidylcholine in the human erythrocyte membrane. A bove a threshold concentration, which was well below the CMC and characteri stic for each detergent, the flip rate increases exponentially upon an incr ease of the detergent concentration in the medium. The detergent-induced fl ip correlates with reported membrane-expanding effects of the detergents at antihemolytic concentrations. From the dependence of the detergent concent ration required for a defined flip acceleration on the estimated membrane v olume, membrane/water partition coefficients for the detergents could be de termined and effective detergent concentrations in the membrane calculated The effective membrane concentrations are similar for most types of deterge nts but are 10-fold lower for octaethylene glycol monoalkyl ether and Trito n X-100. The effectiveness of a given type of detergent is rather independe nt of its alkyl chain length. Since detergents do not reduce the high tempe rature dependence of the flip process the detergent-induced flip is propose d to be due to an enhanced probability of formation of transient hydrophobi c structural defects in the membrane barrier which may result from perturba tion of the interfacial region of the bilayer by inserted detergent molecul es. (C) 2000 Elsevier Science B.V. All rights reserved.