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, ϕtrans, 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 ϕtrans range; 
however, the presence of zinc ion induces DCD-1L to permeabilize the DPTL/DOPS 
tBLM at physiological ϕtrans 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 His(38) residue of the C terminus 
and the carboxyl group of DOPS. Chronocoulometric potential jumps from ϕtrans ≅ 
+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.