We studied the ability of di-cationic gemini surfactantsdi (amphiphiles), i
.e. 1,4-butanediammonium-N,N-dialkyl-N,N,N',N'-tetramethyl bromides (Di-C-m
-diQAS (s = 4), where m = 8,11,13,16 and s = the number of alkyl groups in
the spacer) to induce shape alteration, vesiculation, haemolysis and phosph
atidylserine exposure in human erythrocytes, and to protect erythrocytes ag
ainst hypotonic haemolysis. At high sublytic concentrations the Di-C-m-di-Q
AS (s = 4) amphiphiles rapidly induced echinocytic (spiculated) shapes and
a release of exovesicles, mainly in the form of tubes, from the cell surfac
e. Following 60 min incubation erythrocytes were sphero-echinocytic and a f
ew cells with invaginations/endovesicles were observed. No phosphatidylseri
ne exposure was detected. The haemolytic potency increased with an increase
of the alkyl chain length. At sublytic concentrations the Di-C-m-di-QAS (s
= 4) amphiphiles protected erythrocytes against hypotonic haemolysis. It i
s suggested that the Di-C-m-di-QAS (s = 4) amphiphiles perturb the membrane
in a similar way as single-chain cationic amphiphiles, but that they do no
t easily translocate to the inner membrane leaflet.