title: Engineering Lipid Structure for Recognition of the Liquid Ordered Membrane Phase.
abstract: The selective partitioning of lipid components in phase-separated membranes is essential for domain formation involved in cellular processes. Identifying and tracking the movement of lipids in cellular systems would be improved if we understood how to achieve selective affinity between fluorophore-labeled lipids and membrane assemblies. Here, we investigated the structure and chemistry of membrane lipids to evaluate lipid designs that partition to the liquid ordered (Lo) phase. A range of fluorophores at the headgroup position and lengths of PEG spacer between the lipid backbone and fluorophore were examined. On a lipid body with saturated palmityl or palmitoyl tails, we found that although the lipid tails can direct selective partitioning to the Lophase through favorable packing interactions, headgroup hydrophobicity can override the partitioning behavior and direct the lipid to the disordered membrane phase (Ld). The PEG spacer can serve as a buffer to mute headgroup-membrane interactions and thus improve Lophase partitioning, but its effect is limited with strongly hydrophobic fluorophore headgroups. We present a series of lipid designs leading to the development of novel fluorescently labeled lipids with selective affinity for the Lophase.
authors: Biotechnology and Bioengineering Department, Sandia National Laboratories , Livermore, California 94551, United States.|Department of Biomedical Engineering, The University of Texas at Austin , Austin, Texas 78705, United States.
authors: Stefan S
authors: SS
authors: Bordovsky
authors: Biotechnology and Bioengineering Department, Sandia National Laboratories , Livermore, California 94551, United States.
authors: Christopher S
authors: CS
authors: Wong
authors: Nanosystems Synthesis/Analysis Department, Sandia National Laboratories , Albuquerque, New Mexico 87185, United States.
authors: George D
authors: GD
authors: Bachand
authors: Department of Biomedical Engineering, The University of Texas at Austin , Austin, Texas 78705, United States.
authors: Jeanne C
authors: JC
authors: Stachowiak
authors: Biotechnology and Bioengineering Department, Sandia National Laboratories , Livermore, California 94551, United States.
authors: Darryl Y
authors: DY
authors: Sasaki
mesh_terms: D002021:Buffers; D005456:Fluorescent Dyes / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry*; D021962:Membrane Microdomains / Q000737:chemistry*; D008566:Membranes; D008856:Microscopy, Fluorescence; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D002021:Buffers; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D008563:Membrane Lipids; D011092:Polyethylene Glycols