Interactions of a charged nanoparticle with a lipid membrane: implications for gene delivery

Biophys J. 2011 Mar 2;100(5):1288-97. doi: 10.1016/j.bpj.2010.11.042.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Membrane / chemistry
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Dendrimers / chemistry*
  • Dendrimers / metabolism*
  • Dendrimers / pharmacology
  • Gene Transfer Techniques*
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism*
  • Models, Biological
  • Porosity
  • Static Electricity
  • Thermodynamics
  • Time Factors

Substances

  • Dendrimers
  • Lipid Bilayers
  • PAMAM Starburst