title: Tuning Liposome Membrane Permeability by Competitive Peptide Dimerization and Partitioning-Folding Interactions Regulated by Proteolytic Activity.
abstract: Membrane active peptides are of large interest for development of drug delivery vehicles and therapeutics for treatment of multiple drug resistant infections. Lack of specificity can be detrimental and finding routes to tune specificity and activity of membrane active peptides is vital for improving their therapeutic efficacy and minimize harmful side effects. We describe a de novo designed membrane active peptide that partition into lipid membranes only when specifically and covalently anchored to the membrane, resulting in pore-formation. Dimerization with a complementary peptide efficiently inhibits formation of pores. The effect can be regulated by proteolytic digestion of the inhibitory peptide by the matrix metalloproteinase MMP-7, an enzyme upregulated in many malignant tumors. This system thus provides a precise and specific route for tuning the permeability of lipid membranes and a novel strategy for development of recognition based membrane active peptides and indirect enzymatically controlled release of liposomal cargo.
authors.affiliation: Centre for Biomimetic Sensor Science, School of Materials Science and Engineering, Nanyang Technological University, Research Techno Plaza, 6th storey XFrontiers block, 50 Nanyang Drive, 637553 Singapore.
authors.forename: Seng Koon
authors.initials: SK
authors.lastname: Lim
authors.affiliation: Division of Molecular Physics, Department of Physics, Chemistry and Biology, Linköping University, 581 83 Linköping, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Sandén
authors.affiliation: Division of Molecular Physics, Department of Physics, Chemistry and Biology, Linköping University, 581 83 Linköping, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Selegård
authors.affiliation: Centre for Biomimetic Sensor Science, School of Materials Science and Engineering, Nanyang Technological University, Research Techno Plaza, 6th storey XFrontiers block, 50 Nanyang Drive, 637553 Singapore.
authors.forename: Bo
authors.initials: B
authors.lastname: Liedberg
authors.affiliation: Division of Molecular Physics, Department of Physics, Chemistry and Biology, Linköping University, 581 83 Linköping, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Aili
mesh_terms: D002463:Cell Membrane Permeability; D006801:Humans; D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010539:Permeability; D017510:Protein Folding; D055503:Protein Multimerization
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides