Amphiphiles with single short hydrocarbon chains insert faster into and translocate faster across lipid bilayer membranes

To these surfactants than polarized epithelial cells. We interpret this result to mean that TX-100, DDPS and SDS act mainly at the level of the plasma membrane of the cells probably by causing structural changes at the level of the membrane or even its dissolution, as expected at concentrations close to the surfactant CMC. On the other hand, the cationic surfactants are probably toxic at a more subtle level, toxicity being at concentrations that are not sufficient to cause significant damage to the physical integrity of the membranes. These effects could even be at the intracellular level, conditioned by membrane partitioning and/or translocation across the membranes. The highly ordered apical membranes of fully polarized cells are the only membrane exposed to the surfactants in confluent polarized cell cultures and intact epithelia whereas non-polarized cells have significant amounts of less-ordered membrane domains exposed. For the homologous series of cationic surfactants examined, the results show that the toxicity to mammalian cells was not linearly dependent upon the surfactant hydrophobic chain length. This observation may have complex reasons related to different affinities of the surfactant for the different, possibly multiple, sites of their action. Without precise information concerning these affinities, something that we are working to obtain, any further discussion of this aspect would be speculative. The effect of the polar head group of the cationic surfactants was also evaluated; C12BZK and C12PB, which have the larger polar head groups and more delocalized charge, were between 2 to 5 times more toxic than C12TAB in all cell lines tested. Delocalized charge on the surfactant head group makes its ionic radius considerably larger and reduces the work required for translocation of the polar group from one side of the membrane to the other. Though there have been a very large number of reports concerning the disinfectant properties of surfactants, their mechanism of action is still not fully understood. Attempts to use surfactants in STI prophylaxis Catharanthine sulfate relied upon their capacity to destroy viral and bacterial membranes but did not seem to take into Benzethonium Chloride account, what in hindsight appears all too obvious, that if they destroyed those membranes they would also destroy the membranes of cells of the vaginal epithelium. However, destruction of cell membranes is not the only mechanism of surfactant toxicity as is evidenced in the case of cationic surfactants. As argued above, their toxic effects probably do not involve gross disassembly of the cell membrane but rather some more subtle effects. Candidate mechanisms that have been proposed in the literature include modulation of membrane curvature elastic stress and consequent reduction of membranebound protein activity, alteration of the electrostatic surface potential of membranes, or interaction with anionic polymers in the cytoplasm or cell nucleus following translocation across the cell plasma membrane. Cationic surfactants are known to bind strongly to DNA and RNA and induce drastic conformational changes in the structure of these polymers. The cell viability results obtained with the MTT assay correlated well with the observed release of LDH from the cells. However, in the case of C10TAB and C12TAB, the LD50 values obtained with the LDH leakage assay were slightly but significantly higher than with the MTT assay. This can be explained by the nature of each assay: the LDH leakage assay, which evaluates the loss of intracellular LDH and its release into the culture medium, is an indicator of irreversible cell death either due to cell membrane damage directly caused by the surfactants or due to loss of plasma membrane integrity posterior to cell death due to reasons that have nothing to do with direct membrane damage by the surfactants. On the other hand, the MTT assay evaluates the metabolic capacity of the cell in reducing MTT to formazan. Our results suggest that the molecular targets of the CnTAB surfactants may be different depending on the length of their hydrophobic chain.

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