Direct observation of lipid bilayer disruption by poly(amidoamine) dendrimers

Almut Mecke, Srinivas Uppuluri, Timothy M. Sassanella, Dong Kuk Lee, A. Ramamoorthy, James R. Baker, Bradford G. Orr, Mark M. Banaszak Holl

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200 Citations (Scopus)

Abstract

Atomic force microscopy (AFM) is employed to observe the effect of poly(amidoamine) (PAMAM) dendrimers on 1,2-dimyristoyl-sn-glycero-3- phosphocholine (DMPC) lipid bilayers. Aqueous solutions of generation 7 PAMAM dendrimers cause the formation of holes 15-40 nm in diameter in previously intact bilayers. This effect is observed for two different branch end-groups - amine and carboxyl. In contrast, carboxyl-terminated core-shell tectodendrimer clusters do not create holes in the lipid membrane but instead show a strong affinity to adsorb to the edges of existing bilayer defects. A possible mechanism for the formation of holes in the lipid bilayer is proposed. The dendrimers remove lipid molecules from the substrate and form aggregates consisting of a dendrimer surrounded by lipid molecules. Dynamic light scattering (DLS) measurements as well as 31P NMR data support this explanation. The fact that tectodendrimers behave differently suggests that their cluster-like architecture plays an important role in their interaction with the lipid bilayer.

Original languageEnglish
Pages (from-to)3-14
Number of pages12
JournalChemistry and Physics of Lipids
Volume132
Issue number1
DOIs
Publication statusPublished - 1 Oct 2004
Externally publishedYes

Keywords

  • Atomic force microscopy
  • Core-shell tectodendrimers
  • Drug delivery
  • Lipid bilayers
  • NMR
  • PAMAM dendrimers

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