The Salentinig Research Group has published a new article in Advanced Functional Materials titled “LL-37 Driven Phase Transition and Stacking in Oligolamellar Gram-Negative Bacterial Membrane Models.”

The study investigates how the antimicrobial peptide LL-37 induces structural changes in bacterial membrane models, offering new insights into peptide–membrane interactions.

For more information: https://advanced.onlinelibrary.wiley.com/doi/10.1002/adfm.202532053

Abstract 

Multidrug-resistant Gram-negative bacteria are a growing clinical threat, driving the search for alternative antimicrobial strategies, such as antimicrobial peptide (AMP)- based materials. However, the rational design of such systems remains constrained by simplified membrane models that neglect critical components of the Gram-negative envelope, such as lipopolysaccharides and cardiolipin, and fail to capture its dual-membrane architecture. This work establishes a materials-oriented experimental framework for constructing membrane-mimetic oligolamellar structures that actively integrate the human AMP LL-37. These hierarchically organized assemblies emulate the compositional and structural complexity of the Gram-negative inner and outer membranes and have the potential to serve as tunable soft-matter platforms for the delivery of AMPs. Combining small-angle X-ray scattering, electron microscopy, electrophoretic mobility analysis, and coarse-grained molecular dynamics simulations, we show that LL-37 interacts strongly with cardiolipin, driving phase transitions from multilamellar vesicles to nanoscale assemblies, followed by membrane stacking. This restructuring phenomenon is unlikely to occur in conventional single-bilayer systems. In the presence of lipopolysaccharides, polysaccharide side chains modulate but do not suppress this transition, revealing a lipid-specific reorganisation mechanism relevant to the design of AMP-based materials targeting Gram-negative bacteria.