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Switching Cytolytic Nanopores into Antimicrobial Fractal Ruptures by a Single Side Chain Mutation.
Katharine Hammond1,2, Flaviu Cipcigan3, Kareem Al Nahas4
1National Physical Laboratory, Hampton Road, Teddington, TW11 0LW, U.K.
ACS Nano
|April 22, 2021
Summary
A single mutation in helical peptides creates novel fractal membrane rupture patterns. These patterns, unlike traditional pores, are nonhemolytic and antimicrobial, offering new nanoscale therapeutic possibilities.
Area of Science:
- Biophysics
- Molecular Biology
- Materials Science
Background:
- Cell membrane disruption is a key host defense mechanism.
- Typically, this involves forming circular nanopores via energetically favorable processes.
- Ultrashort helical peptides are known to form transmembrane pores.
Purpose of the Study:
- To investigate the effect of a single side-chain mutation on ultrashort helical peptide membrane disruption.
- To characterize the novel rupture patterns induced by this mutation.
- To compare the antimicrobial and hemolytic properties of the new disruption mode with traditional pore formation.
Main Methods:
- Utilized ultrashort helical peptides (8-11-mers) with a specific side-chain mutation.
- Observed membrane disruption patterns using advanced nanoscale imaging techniques.
- Assessed antimicrobial activity and hemolytic potential of the peptides.
Main Results:
- A single mutation induced an elaborate fractal rupture pattern, distinct from circular nanopores.
- This fractal disruption was confined to the upper leaflet of the lipid bilayer.
- The fractal rupture exhibited propagating fronts resembling viscous fluid instabilities.
- Both pore and fractal disruption modes showed antimicrobial properties.
- Fractal rupture was nonhemolytic, unlike pore formation.
Conclusions:
- A single amino acid change can drastically alter peptide-induced membrane disruption mechanisms.
- Fractal membrane rupture represents a novel, nonhemolytic antimicrobial mechanism.
- These findings have significant implications for designing targeted nanoscale therapeutics with reduced side effects.
