liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Tuning Liposome Membrane Permeability by Competitive Peptide Dimerization and Partitioning-Folding Interactions Regulated by Proteolytic Activity
Nanyang Technology University, Singapore.
Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0002-1781-1489
Nanyang Technology University, Singapore.
Show others and affiliations
2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 21123, p. 1-9Article in journal (Refereed) Published
Resource type
Text
Abstract [en]

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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2016. Vol. 6, no 21123, p. 1-9
National Category
Physical Sciences Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-126131DOI: 10.1038/srep21123ISI: 000370532500002PubMedID: 26892926OAI: oai:DiVA.org:liu-126131DiVA, id: diva2:912071
Note

Funding Agencies|Linkoping University; Swedish Research Council (VR); Swedish Foundation for Strategic Research (SSF); Knut and Alice Wallenberg Foundation (KAW); Centre in Nanoscience and Technology (CeNano); Provost Office, NTU

Available from: 2016-03-15 Created: 2016-03-15 Last updated: 2019-01-22
In thesis
1. Peptide-Liposome Model Systems for Triggered Release
Open this publication in new window or tab >>Peptide-Liposome Model Systems for Triggered Release
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Liposomes are widely used in drug delivery to improve drug efficacy and to reduce side effects. For liposome-encapsulated drugs to become bioavailable and provide a therapeutic effect they must be released, which typically is a slow process that primarily relies on passive diffusion, liposome rupture or endocytotic uptake. Achieving drug concentrations within the therapeutic window can thus be challenging, resulting in poor efficacy and higher risks drug resistance. Finding means to modulate lipid membrane integrity and to trigger rapid and efficient release of liposomal cargo is thus critical to improve current and future liposomal drug delivery systems. The possibilities to tailor lipid composition and surface functionalization is vital for drug delivery applications but also make liposomes attractive model systems for studies of membrane active biomolecules.

The overall aim of this thesis work has been to develop new strategies for triggering and controlling changes in lipid membrane integrity and to study the interactions of membrane active peptides with model lipid membranes using both de novo designed and biologically derived synthetic amphipathic cationic peptides. Two different sets of designed peptides have been explored that can fold and heterodimerize into a coiled coil and helix-loop-helix fourhelix bundle, respectively. Conjugation of the cationic lysine rich peptides to liposomes triggered a rapid and concentration dependent release. The additions of their corresponding glutamic acid-rich complementary peptides inhibited the release of liposomal cargo. Possibilities to reduce the inhibitory effect by both proteolytic digestion of the inhibitory peptide and by means of heterodimer exchange have been investigated. Moreover, the effects of peptide size and composition and ability to fold have been studied in order to elucidate the factors that influence the membrane permeabilizing effects of the peptides.

In addition, the membrane activity of a the two-peptide bacteriocin PLNC8α and PLNC8β has been explored using liposomes as a model system. PLNC8αβ are expressed by Lactobacillus plantarum and were shown to display pronounced membrane-partition folding coupling, leading to rapid release of liposome encapsulated carboxyfluorescein. PLNC8αβ also kill and suppressed growth of the gram-negative bacteria Porphyromonas gingivalis by efficiently damaging the bacterial membrane.

Although membrane active peptides are highly efficient in perturbing lipid membrane integrity, possibilities to trigger release using external stimuli are also of large interest for therapeutic applications. Light-induced heating of liposome encapsulated gold nanoparticles (AuNPs) has been shown by others as a potential strategy to trigger drug release. To facilitate fabrication of thermoplasmonic liposome systems we developed a simple method for synthesis of small AuNPs inside liposomes, using the liposomes as nanoscale reaction vessels.

The work presented in this thesis provides new knowledge and techniques for future development of liposome-based drug delivery systems, peptide-based therapeutics and increase our understanding of peptide-lipid interactions.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2018. p. 78
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1922
National Category
Biophysics Biomaterials Science Biochemistry and Molecular Biology Physical Chemistry
Identifiers
urn:nbn:se:liu:diva-150419 (URN)10.3384/diss.diva-150419 (DOI)978-91-7685-337-5 (ISBN)
Public defence
2018-09-21, Planck, Fysikhuset, Campus Valla, Linköping, 09:15 (English)
Opponent
Supervisors
Available from: 2018-08-22 Created: 2018-08-22 Last updated: 2018-09-12Bibliographically approved

Open Access in DiVA

fulltext(959 kB)145 downloads
File information
File name FULLTEXT01.pdfFile size 959 kBChecksum SHA-512
647f161094937ef16335bf4f4df0340481df995ab5b2b2e4cac4b7c3631a79dfbe77465581b889a14d09274b51c5d10e6c87218d6c33951447e18f90c71b9067
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Sandén, CamillaSelegård, RobertLiedberg, BoAili, Daniel

Search in DiVA

By author/editor
Sandén, CamillaSelegård, RobertLiedberg, BoAili, Daniel
By organisation
Molecular PhysicsFaculty of Science & Engineering
In the same journal
Scientific Reports
Physical SciencesBiochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 145 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 640 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf