We propose classifying surfactants with respect to their effect on membrane order, which is derived from the time-resolved fluorescence anisotropy of DPH. This may help in understanding why certain surfactants, including biosurfactants such as antimicrobial lipopeptides and saponins, often show a superior performance to permeabilize and lyse membranes and/or a better suitability for membrane protein solubilization. Micelle-forming surfactants induce curvature stress in membranes that causes disordering and, finally, lysis. Typical detergents such as C(12)EO(8), octyl glucoside, SDS, and lauryl maltoside initiate membrane lysis after reaching a substantial, apparently critical extent of disordering. In contrast, the fungicidal lipopeptides surfactin, fengycin, and iturin from Bacillus subtilis QST713 as well as digitonin, CHAPS, and lysophosphatidylcholine solubilize membranes without substantial, overall disordering. We hypothesize they disrupt the membrane locally due to a spontaneous segregation from the lipid and/or packing defects and refer to them as heterogeneously perturbing. This may account for enhanced activity, selectivity, and mutual synergism of antimicrobial biosurfactants and reduced destabilization of membrane proteins by CHAPS or digitonin. Triton shows the pattern of a segregating surfactant in the presence of cholesterol.

No abstract

treated with pHLIP-K(rho)C(aph) also showed signs of cytoskeletal immobilization, consistent with the knowledge that phalloidin binds to F-actin and stabilizes the filament against depolymerization. However, the antiproliferative effect was not observed with pHLIP-C(aph). The insertion behavior of both constructs were studied in POPC liposomes using Trp fluorescence: pHLIP-K(rho)C(aph) and pHLIP-C(aph) insert with the same apparent pK of 6.1-6.2, similar to that of pHLIP (without any cargo). However, kinetic experiments suggest that pHLIP-C(aph) inserts much slower than pHLIP-K(rho)C(aph), possibly accounting for its lack of antiproliferative effects in cell assays. In short, our results obtained with pHLIP-K(rho)C(aph) lay the foundation for the development of a new class of anti-tumor agents that would selectively enter and destroy cancer cells while not affecting normal cells. Such pHLIPmediated delivery of otherwise cell-impermeable agents may enhance the efficacy of treatment, as well as significantly reducing the side effect.