Mode-of-action ofantimicrobialpeptides: membrane disruption vs intracellular mechanisms Antimicrobial peptides (AMPs) are a crucial component of innate immunity, actively killing microbes and preventing infection through various mechanisms.作者：L Chen·2013·被引用次数：21—In this model, thepeptides spread on the surface of the membrane and cover the surface like a carpet. At high peptide concentration, some peptides insert and ... Among these, the carpet model offers a significant explanation for how certain AMPs disrupt bacterial cell membranes. This model posits that AMPs first accumulate on the membrane surface, covering it like a carpet, before inducing membrane permeabilization or disintegration. Understanding this mechanism is vital for developing new therapeutic strategies against resistant infections.
The carpet model describes a non-pore-forming mechanism for AMP action. Unlike models that involve peptides forming distinct pores within the membrane, the carpet mechanism relies on a high concentration of peptides aggregating on the membrane's outer surface. This aggregation is often driven by electrostatic interactions between the positively charged peptides and the negatively charged membrane lipids.
Once a critical threshold concentration is reached, the peptides begin to disrupt the lipid bilayer. This disruption can occur through several proposed pathways:
* Membrane Destabilization: The sheer number of peptides on the surface can destabilize the membrane's integrity, leading to increased fluidity and eventual rupture.
* Detergent-like Action: Some AMPs acting via the carpet model may exhibit detergent-like properties, solubilizing the membrane lipids and causing its breakdown.
* Permeabilization: The accumulated peptides can induce transient pores or increase membrane permeability, allowing cellular contents to leak out and the cell to die.
Peptide monomers adhere parallel to the membrane surface, with their hydrophilic ends facing the solution and hydrophobic ends interacting with the lipid bilayerMembrane permeation by the carpet model. Antimicrobial .... This arrangement is key to forming the "carpet" effect.
Several AMPs are understood to act through the carpet mechanism. For instance, peptides like Aurein 1.2, Citropin 1.From “carpet” mechanism to de-novo designed ...1, and Maculatin 1.1 have predominantly shown a carpet mechanism against biological lipid membranes (BLMs). The effectiveness and specific mode of disruption can depend on factors such as peptide structure, concentration, and the specific lipid composition of the target membrane.Antimicrobial peptides(AMPs) are being studied for their potential in addressing microbial resistance, a significant issue in treating infections. More than ...
While the carpet model is a distinct mechanism, it's also important to note that some AMPs might transition between different mechanisms. For example, research has explored the potential "carpet-to-barrel" or toroidal-pore transition, suggesting that an initial carpet-like accumulation could, under certain conditions, lead to pore formationIn the carpet model, the cationic AMPs first bind to the membrane surface via electrostatic interactions and cover it in a carpet-like manner.. This highlights the complexity and dynamic nature of AMP-membrane interactions.Membrane Active Antimicrobial Peptides: Translating ...
The carpet model stands in contrast to other proposed mechanisms of AMP action, most notably the pore-forming models.
* Barrel-Stave Pore Model: In this model, amphipathic peptides insert into the membrane and aggregate with their hydrophobic faces inward, forming a transmembrane pore.
* Toroidal Pore Model: Here, peptides insert into the membrane and line the pore, with the lipid head groups and polar ends of the peptides also forming part of the pore liningPeptide–membrane interactions and mechanisms of ....
The carpet model, by contrast, emphasizes disruption through peptide accumulation and destabilization rather than the formation of discrete, ordered pores. The high concentration of peptides required for membrane permeation and disintegration in the carpet model provides strong support for this non-pore-forming mechanism.
The carpet model provides a crucial framework for understanding how AMPs exert their antimicrobial effects. By elucidating these mechanisms, researchers can better design synthetic peptides with enhanced efficacy and specificity, potentially leading to new therapeutic agents to combat antibiotic-resistant bacteria.Antimicrobial peptides are described with the carpet model. Such peptides permeabilize membranes by “carpeting” the bilayer with peptides. At high ... Further research continues to refine our understanding of AMP-membrane interactions, exploring variations within the carpet mechanism and its interplay with other modes of action. This deeper insight is essential for harnessing the full therapeutic potential of antimicrobial peptides.
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