Chiral lipid bilayers are enantioselectively permeable

Nat Chem. 2021 Aug;13(8):786-791. doi: 10.1038/s41557-021-00708-z. Epub 2021 Jun 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkynes / chemistry
  • Alkynes / metabolism
  • Amino Acids / chemistry
  • Amino Acids / metabolism
  • Cholesterol / chemistry
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism*
  • Permeability
  • Phosphatidylcholines / chemistry
  • Stereoisomerism

Substances

  • Alkynes
  • Amino Acids
  • Fluorescent Dyes
  • Lipid Bilayers
  • Phosphatidylcholines
  • Cholesterol
  • 1,2-oleoylphosphatidylcholine
  • 1-palmitoyl-2-oleoylphosphatidylcholine