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Membrane Transport Processes Analyzed by a Highly Parallel Nanopore Chip System at Single Protein Resolution
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Water-templated transmembrane nanopores from shape-persistent oligocholate macrocycles.

Hongkwan Cho1, Lakmini Widanapathirana, Yan Zhao

  • 1Department of Chemistry, Iowa State University, Ames, Iowa 50011-3111, USA.

Journal of the American Chemical Society
|December 15, 2010
PubMed
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Macrocyclic oligocholates self-assemble into nanopores in lipid membranes by attracting water, defying typical hydrophobic effects. This assembly surprisingly enhances membrane permeability for molecules like glucose and maltotriose.

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Area of Science:

  • Biophysical chemistry
  • Membrane biophysics
  • Supramolecular chemistry

Background:

  • Hydrophobic interactions typically disfavor self-assembly in hydrophobic environments.
  • Macrocyclic oligocholates are compounds with potential self-assembly properties.
  • Lipid membranes present a hydrophobic barrier to molecule transport.

Purpose of the Study:

  • To investigate the self-assembly behavior of macrocyclic oligocholates in lipid membranes.
  • To understand the role of water molecules in this self-assembly process.
  • To explore the impact of this self-assembly on membrane permeability and transport.

Main Methods:

  • Incorporation of macrocyclic oligocholates into lipid membranes.
  • Observation of self-assembly into transmembrane nanopores.
  • Measurement of membrane permeability for various hydrophilic molecules (glucose, maltotriose).
  • Assessment of cholesterol's effect on membrane properties and transport.

Main Results:

  • Macrocyclic oligocholates self-assembled into nanopores by templating aggregated water molecules within the hydrophobic membrane.
  • This self-assembly process was driven by an unusual, counterintuitive hydrophobic effect.
  • Membrane permeability to glucose significantly increased with cholesterol inclusion.
  • The cyclic cholate tetramer showed higher permeability for maltotriose than glucose.

Conclusions:

  • Water aggregation in hydrophobic environments can drive self-assembly of macrocycles into functional nanopores.
  • This self-assembly mechanism leads to unexpected alterations in membrane transport properties.
  • Cholesterol can enhance the permeability of oligocholate-containing membranes, contrary to its usual effect.
  • The size selectivity of these novel nanopores warrants further investigation.