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

doi:10.1016/j.chemphyslip.2004.09.001

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

Dept. of Fine Chemistry

University of Michigan, Ann Arbor

Research output: Contribution to journal › Article › peer-review

229 Scopus citations

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 language	English
Pages (from-to)	3-14
Number of pages	12
Journal	Chemistry and Physics of Lipids
Volume	132
Issue number	1
DOIs	https://doi.org/10.1016/j.chemphyslip.2004.09.001
State	Published - Oct 2004

Keywords

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

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10.1016/j.chemphyslip.2004.09.001

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title = "Direct observation of lipid bilayer disruption by poly(amidoamine) dendrimers",

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.",

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author = "Almut Mecke and Srinivas Uppuluri and Sassanella, \{Timothy M.\} and Lee, \{Dong Kuk\} and A. Ramamoorthy and Baker, \{James R.\} and Orr, \{Bradford G.\} and \{Banaszak Holl\}, \{Mark M.\}",

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language = "English",

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AU - Mecke, Almut

AU - Uppuluri, Srinivas

AU - Sassanella, Timothy M.

AU - Lee, Dong Kuk

AU - Ramamoorthy, A.

AU - Baker, James R.

AU - Orr, Bradford G.

AU - Banaszak Holl, Mark M.

PY - 2004/10

Y1 - 2004/10

N2 - 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.

AB - 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.

KW - Atomic force microscopy

KW - Core-shell tectodendrimers

KW - Drug delivery

KW - Lipid bilayers

KW - NMR

KW - PAMAM dendrimers

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DO - 10.1016/j.chemphyslip.2004.09.001

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C2 - 15530443

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SN - 0009-3084

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EP - 14

JO - Chemistry and Physics of Lipids

JF - Chemistry and Physics of Lipids

IS - 1

ER -

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

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