The mechanism of membrane permeabilization by dermcidin (DCD-1L), an antimicrobial peptide present in human sweat, was investigated at a mercury-supported monolayer of dioleoylphosphatidylcholine (DOPC) or dioleoylphosphatidylserine (DOPS) and at a mercury-supported tethered bilayer lipid membrane (tBLM) consisting of a thiolipid (DPTL) with a DOPC or DOPS monolayer self-assembled on top of it. In an unbuffered solution of pH 5.4, DCD-1L is almost neutral and permeabilizes a DPTL/DOPS tBLM at transmembrane potentials, ϕ_trans, which are physiological. In a pH 7 buffer solution DCD-1L bears two negative charges and has no effect on a DPTL/DOPC tBLM, whereas it permeabilizes a DPTL/DOPS tBLM only outside the physiological ϕ_trans range; however, the presence of zinc ion induces DCD-1L to permeabilize the DPTL/DOPS tBLM at physiological ϕ_trans values. The effect of zinc ions suggests a DCD-1L conformation with its positive N-terminus embedded in the lipid bilayer and the negative C terminus floating on the membrane surface. This conformation can be stabilized by a zinc ion bridge between the His³⁸ residue of the C terminus and the carboxyl group of DOPS. Chronocoulometric potential jumps from ϕ_trans ≅ +160 mV to sufficiently negative values yield charge transients exhibiting a sigmoidal shape preceded by a relatively long “foot”. This behavior is indicative of ion-channel formation characterized by disruption of DCD-1L clusters adsorbed on top of the lipid bilayer, incorporation of the resulting monomers and their aggregation into hydrophilic pores by a mechanism of nucleation and growth.

Monolayers and bilayers of lipid mixtures self-assembled on mercury form spontaneously gel-phase (solid ordered, s_o) and liquid-ordered (l_o) microdomains, thanks to the fluidity imparted to these films by the liquid metal support. The differential capacity of the hydrocarbon tail region of monolayers of mixtures of two lipid components of high and low transition temperature T_m , increases during the transition from the liquid disordered (l_d) phase to the coexistence of l_d and s_o phases. Addition of cholesterol to this binary mixture causes a decrease in differential capacity. This behavior is explained by regarding the capacity as a measure of the total perimeter of the s_o microdomains, due to the mismatch between these microdomains and the l_d phase. Cholesterol removes this mismatch by converting the anisotropic s_o microdomains into isotropic l_o microdomains (rafts). This allows differential capacity measurements by electrochemical impedance spectroscopy to follow phase transitions in lipid mixtures. The coexistance of l_d, l_o and s_o phases is confirmed by images of a distal lipid monolayer self-assembled on top of a thiolipid monolayer tethered to a mercury microcap, by using two-photon fluorescence lifetime imaging microscopy (2P-FLIM).