Calcium mediated DNA binding in non-lamellar structures formed by DOPG/glycerol monooleate

Chem Phys Lipids. 2021 Sep:239:105118. doi: 10.1016/j.chemphyslip.2021.105118. Epub 2021 Jul 16.

Abstract

In order to test an encapsulation method of short fragmented DNA (∼ 20-300 bp), we study the solubilisation in 150 mM solution of NaCl of a cubic phase formed by glycerol monooleate (GMO) with negatively charged dioleoylphosphatidylglycerol (DOPG) up to the level of unilamellar vesicles and, subsequently, the restoration of the cubic phase using Ca2+ cations. We performed small angle X-ray and neutron scattering (SAXS and SANS) to follow structural changes in DOPG/GMO mixtures induced by increasing DOPG content. The cubic phase (Pn3m space group) is preserved up to ∼ 11 mol% of DOPG in DOPG/GMO. Above 20 mol%, the SANS curves are typical of unilamellar vesicles. The thickness of the DOPG/GMO lipid bilayer (dL) decreases slightly with increasing fraction of DOPG. The addition of 15 mM of CaCl2 solution shields the electrostatic repulsions of DOPG molecules, increases slightly dL and restores the cubic structures in the mixtures up to ∼ 37 mol% of DOPG. Zeta potential shows negative surface charge. The analysis of the data provides the radius of the water nano-channels of the formed non-lamellar structures. We discuss their dimensions with respect to DNA binding. In addition, Ca2+ mediates DNA - DOPG/GMO binding. The formed hexagonal phase, HII, binds less of DNA in comparison with cubic phases (∼ 6 wt% and ∼ 20 wt% of the total amount, respectively). The studied system can be utilized as anionic QII delivery vector for genetic material.

Keywords: Calcium; DNA; DOPG; Glycerol monooleate; SANS; SAXS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / chemistry*
  • DNA / chemistry*
  • DNA / metabolism
  • Glycerides / chemistry
  • Lipid Bilayers / chemistry*
  • Lipid Bilayers / metabolism
  • Phosphatidylglycerols / chemistry
  • Scattering, Small Angle
  • Water / chemistry
  • X-Ray Diffraction

Substances

  • Glycerides
  • Lipid Bilayers
  • Phosphatidylglycerols
  • Water
  • 1,2-dioleoyl-sn-glycero-3-phosphoglycerol
  • DNA
  • monoolein
  • Calcium