LL-37

LL-37 is produced primarily by neutrophils, NK cells, mast cells, and epithelial cells of the skin, gut, and respiratory tract. It is a front-line component of the innate immune defense, released rapidly at sites of infection or injury before adaptive immune responses are mobilized. Its name derives from its 37-amino-acid length and N-terminal Leucine-Leucine (LL) sequence.

Beyond direct antimicrobial activity, LL-37 has important immunomodulatory roles: it neutralizes bacterial LPS (preventing septic shock), triggers dendritic cell maturation, and acts as a chemoattractant for immune cells. It also promotes angiogenesis and re-epithelialization in wound healing — making it a multi-functional innate defense effector rather than a simple antibiotic.

// MEMBRANE DISRUPTION

LL-37 adopts an amphipathic α-helical structure in hydrophobic environments (bacterial membranes), allowing its positively charged face to electrostatically bind anionic bacterial phospholipids. It then inserts into and disrupts the membrane via a "carpet model" — disintegrating the lipid bilayer at high concentrations rather than forming discrete pores.

// BIOFILM DISRUPTION

Unlike most conventional antibiotics, LL-37 can penetrate and disrupt established biofilms of Pseudomonas aeruginosa, S. aureus, and E. coli at sub-inhibitory concentrations by interfering with quorum sensing (via autoinducer binding) and destabilizing biofilm matrix polysaccharides.

// LPS NEUTRALIZATION

LL-37 binds lipopolysaccharide (LPS/endotoxin) from gram-negative bacteria with high affinity, preventing LPS from engaging TLR4 on macrophages and avoiding the catastrophic cytokine storm of septic shock. This makes LL-37 a candidate for sepsis intervention.