Potent macromolecule-sized poration of lipid bilayers by the macrolittins, a synthetically evolved family of pore-forming peptides

Sijia Li, Sarah Y. Kim, Anna E. Pittman, Gavin M. King, William C. Wimley, Kalina A Hristova

Research output: Contribution to journalArticle

Abstract

Pore-forming peptides with novel functions have potential utility in many biotechnological applications. However, the sequence-structure-function relationships of pore forming peptides are not understood well enough to empower rational design. Therefore, in this work we used synthetic molecular evolution to identify a novel family of peptides that are highly potent and cause macromolecular poration in synthetic lipid vesicles at low peptide concentration and at neutral pH. These unique 26-residue peptides, which we call macrolittins, release macromolecules from lipid bilayer vesicles made from zwitterionic PC lipids at peptide to lipid ratios as low as 1:1000, a property that is almost unprecedented among known membrane permeabilizing peptides. The macrolittins exist as membrane-spanning α-helices. They cause dramatic bilayer thinning and form large pores in planar supported bilayers. The high potency of these peptides is likely due to their ability to stabilize bilayer edges by a process that requires specific electrostatic interactions between peptides.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StateAccepted/In press - Mar 19 2018

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of 'Potent macromolecule-sized poration of lipid bilayers by the macrolittins, a synthetically evolved family of pore-forming peptides'. Together they form a unique fingerprint.

  • Cite this