NKCS, a Mutant of the NK-2 Peptide, Causes Severe Distortions and Perforations in Bacterial, But Not Human Model Lipid Membranes

Abstract

NKCS is an improved mutant of the bioactive peptide NK-2, which shows strong activity against Escherichia coli and low toxicity towards human cells. The different activity demonstrates the relevance of the physico-chemical nature of the target membrane for the biological effect of this peptide. We studied the effect of this potent antimicrobial peptide on model membranes by activity studies, differential scanning calorimetry, single molecule tracking and tracer efflux experiments. We found that NKCS severely distorted, penetrated and perforated model lipid membranes that resembled bacterial membranes, but not those that were similar to human cell membranes. The interactions of NKCS with phosphatidylethanolamine, which is abundant in bacterial membranes, were especially strong and are probably responsible for its antimicrobial activity.

Comparison of patient-derived high and low phosphatidylserine-exposing colorectal carcinoma cells in their interaction with anti-cancer peptides

“…We observed PS‐dependent enhanced peptide binding to (Zeta potential measurements) as well as peptide insertion into (Trp fluorescence analysis) lipid model membranes constituted of zwitterionic PC and PS, reflecting the outward‐facing leaflet of cancer human cells. This is fully compliant with various former investigations where only minor to completely absent interactions of peptide NK‐2 with pure PC model membranes have been repeatedly proven . This is in contrast to melittin, where no such dependence could be observed.…”

The penetrating properties of the tumor homing peptide LyP‐1 in model lipid membranes

“…TAT peptide, a typical CPP, did not translocate the GUVs containing zwitterionic PC lipids in the same experimental conditions, although it was highly positively charged, with six arginine and two lysine amino acid residues. However, HIV1 TAT accumulated on neutral membranes as in the case of the cyclic LyP‐1 peptide while tLyP‐1 showed neither accumulation nor internalization in PC membranes, similar to antimicrobial peptides …”

“…However, HIV1 TAT accumulated on neutral membranes as in the case of the cyclic LyP-1 peptide while tLyP-1 showed neither accumulation nor internalization in PC membranes, similar to antimicrobial peptides. 31 To get further insight into the role played by lipid composition on the mode of action of the investigated peptides on model membranes, we incubated either tLyP-1 or LyP-1 peptides with anionic GUVs containing different percentages of DOPS. Experimental results showed that tLyP-1 peptide strongly accumulated on the membranes and the accumulation was higher than in case of LyP-1 (Figures 2, 4B, and S2).…”

Bioinspired Nanoemulsions Stabilized by Phosphoethanolamine and Phosphoglycerol Lipids

“…PEs are reported to have HLB values around 6, while PGs’ HLB values are even lower [ 27 , 28 ]; hence their mixtures are expected to have HLB values which would promote their use as inverted emulsion stabilizers. Moreover, the PLs mixture employed is characterized by a thermotropic phase transition of the lipid microscopic arrangement from a gel phase to a fluid liquid crystalline phase at 18 °C [ 29 ]. Therefore, at 25 °C (i.e., our experimental temperature), PLs are in a fluid liquid crystalline phase thus potentially providing a major stability by wrapping the dispersed emulsion droplets in a viscous liquid crystalline matrix [ 30 ].…”