LL‐37 Driven Phase Transition and Stacking in Oligolamellar Gram‐Negative Bacterial Membrane Models
Year: 2026
Type: article
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. These results deepen mechanistic understanding of AMP‐membrane interactions and establish design principles for peptide‐integrated soft materials with programmable structural responses. The presented platform further enables the development of antimicrobial biointerfaces through targeted membrane remodeling.
Source: Advanced Functional Materials
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,790
OpenAlex ID: W7135012349