LL-37: How a tiny peptide carries out its great responsibility in the innate immune system

Nguyen Thi Huong Xuan, Tran Tong Khanh Linh, Phan Hoang Thien An, Nguyen Tan Khoi

Abstract


Elucidating the mode of action of antimicrobial peptides (AMPs) in cell membrane disruption is a topic of interest in understanding the efficiency of different AMPs, which is beneficial in designing antibiotics with desired potency and selectivity. As a key component of the innate immunity system, human cathelicidin LL-37 plays a crucial role in protecting human against infectious diseases. LL-37 kills cells by disrupting the membrane integrity through physical interaction with cell membranes. In this paper, we investigated the molecular interactions of LL-37 with various model cell membranes using Sum Frequency Generation (SFG), a modern vibrational spectroscopic technique. 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPG) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) supported bilayers were used as models for bacterial cell membranes and mammalian cell membranes, respectively. In our experiments, the helical
LL-37 molecules associated with the POPG/POPG bilayer surface at a tilt angle of 50o from the bilayer normal, indicating a toroidal pore mechanism of action for the peptide at a concentration of 400 nM. On the contrary, no interactions were observed between LL-37 and a zwitterionic POPC bilayer at much higher peptide concentrations (∼1.2 μM). Cholesterol is shown to suppress peptide-induced disorder in the lipid bilayer membranes.  These results would explain a selective effect of LL-37 on bacteria over mammalian cells. Additionally, in order to deduce the orientation of LL-37 on model cell membranes, we have introduced a modified data analysis approach. Our findings demonstrate that SFG is a powerful technique which can provide insights into the molecular interactions between antimicrobial peptides possessing multiple helical segments and cell membranes.

 


Keywords


LL-37, cathelicidin peptide, model cell membranes, peptide-membrane interaction.



DOI: https://doi.org/10.15625/2615-9023/v40n2se.11576 Display counter: Abstract : 109 views.

 

                 

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