Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Conformational Aspects of High Content Packing of Antimicrobial Peptides in Polymer Microgels

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Remote Loading of (64)Cu(2+) into Liposomes without the Use of Ion Transport Enhancers

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Concentration- and pH-Dependent Oligomerization of the Thrombin-Derived C-Terminal Peptide TCP-25

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Thrombin-derived C-terminal fragments aggregate and scavenge bacteria and their proinflammatory products

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. A C-terminal peptide of TFPI-1 facilitates cytosolic delivery of nucleic acid cargo into mammalian cells

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. A dual-action peptide-containing hydrogel targets wound infection and inflammation

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Degradable dendritic nanogels as carriers for antimicrobial peptides

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Shalini Singh
  • Aritreyee Datta
  • Bruno C Borro
  • Mina Davoudi
  • Artur Schmidtchen
  • Anirban Bhunia
  • Martin Malmsten
Vis graf over relationer

Successful use of microgels as delivery systems of antimicrobial peptides (AMPs) requires control of factors determining peptide loading and release to/from the microgels as well as of membrane interactions of both microgel particles and released peptides. Addressing these, we here investigate effects of microgel charge density and conformationally induced peptide amphiphilicity on AMP loading and release using detailed nuclear magnetic resonance (NMR) structural studies combined with ellipsometry, isothermal titration calorimetry, circular dichroism, and light scattering. In parallel, consequences of peptide loading and release for membrane interactions and antimicrobial effects were investigated. In doing so, poly(ethyl acrylate-co-methacrylic acid) microgels were found to incorporate the cationic AMPs EFK17a (EFKRIVQRIKDFLRNLV) and its partially d-amino acid-substituted variant EFK17da (E(dF)KR(dI)VQR(dI)KD(dF)LRNLV). Peptide incorporation was found to increase with increasing with microgel charge density and peptide amphiphilicity. After microgel incorporation, which appeared to occur preferentially in the microgel core, NMR showed EFK17a to form a helix with pronounced amphiphilicity, while EFK17da displayed a folded conformation, stabilized by a hydrophobic hub consisting of aromatic/aromatic and aliphatic/aromatic interactions, resulting in much lower amphiphilicity. Under wide ranges of peptide loading, the microgels displayed net negative z-potential. Such negatively charged microgels do not bind to, nor lyse, bacteria-mimicking membranes. Instead, membrane disruption in these systems is mediated largely by peptide release, which in turn is promoted at higher ionic strength and lower peptide amphiphilicity. Analogously, antimicrobial effects against Escherichia coli were found to be dictated by peptide release. Taken together, the findings show that peptide loading, packing, and release strongly affect the performance of microgels as AMP delivery systems, effects that can be tuned by (conformationally induced) peptide amphiphilicity and by microgel charge density.

OriginalsprogEngelsk
TidsskriftACS applied materials & interfaces
Vol/bind9
Udgave nummer46
Sider (fra-til)40094-40106
Antal sider13
ISSN1944-8244
DOI
StatusUdgivet - 22 nov. 2017

ID: 52418505