Chiral lipid bilayers are enantioselectively permeable

  • Nat Chem. 2021 Aug;13(8):786-791. doi: 10.1038/s41557-021-00708-z.
Juan Hu  1 ,  Wesley G Cochrane  1 ,  Alexander X Jones  2 ,  Donna G Blackmond  2 ,  Brian M Paegel  3  4
Affiliations
  • 1. Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA.
  • 2. Department of Chemistry, Scripps Research, La Jolla, CA, USA.
  • 3. Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA. [email protected].
  • 4. Departments of Chemistry and Biomedical Engineering, University of California, Irvine, CA, USA. [email protected].
PMID: 34112989 DOI: 10.1038/s41557-021-00708-z
Abstract

Homochiral membrane bilayers organize biological functions in all domains of life. The membrane's permeability-its key property-correlates with a molecule's lipophilicity, but the role of the membrane's rich and uniform stereochemistry as a permeability determinant is largely ignored in empirical and computational measurements. Here, we describe a new approach to measuring permeation using continuously generated microfluidic droplet interface bilayers (DIBs, generated at a rate of 480 per minute) and benchmark this system by monitoring Fluorescent Dye DIB permeation over time. Enantioselective permeation of alkyne-labelled Amino acids (Ala, Val, Phe, Pro) and dipeptides through a chiral phospholipid bilayer was demonstrated using DIB transport measurements; the biological L enantiomers permeated faster than the D enantiomers (from 1.2-fold to 6-fold for Ala to Pro). Enantioselective permeation both poses a potentially unanticipated criterion for drug design and offers a kinetic mechanism for the abiotic emergence of homochirality via chiral transfer between sugars, Amino acids and lipids.

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