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Published March 2, 2011 | public
Journal Article

Interactions of a Charged Nanoparticle with a Lipid Membrane: Implications for Gene Delivery


We employ self-consistent field theory to study the thermodynamics of membrane-particle interactions in the context of gene delivery systems, with the aim to guide the design of dendrimers that can overcome the endosomal escape barrier by inserting into membranes and creating pores. We consider the interaction between a model polyamidoamine dendrimer and a membrane under controlled tension as a function of the separation between the dendrimer and the membrane. In all the cases we have studied, the lowest free energy state corresponds to the membrane partially wrapping the dendrimer. However, with moderate tension, we find that a G5 (or larger) generation dendrimer, through thermal fluctuation, can induce the formation of metastable pores. These metastable pores are subsequently shown to significantly lower the critical tension necessary for membrane rupture, thus possibly enhancing the release of the trapped genetic material from the endosome.

Additional Information

© 2011 Biophysical Society. Received 24 September 2010; accepted 23 November 2010. Editor: Ka Yee C. Lee.. Available online 1 March 2011. The authors gratefully acknowledge support from the Jacobs Institute for Molecular Engineering for Medicine at Caltech. C.L.T. is thankful for financial support from a National Institutes of Health training grant.

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