title: Targeting proteins to liquid-ordered domains in lipid membranes.
abstract: We demonstrate the construction of novel protein-lipid assemblies through the design of a lipid-like molecule, DPIDA, endowed with tail-driven affinity for specific lipid membrane phases and head-driven affinity for specific proteins. In studies performed on giant unilamellar vesicles (GUVs) with varying mole fractions of dipalymitoylphosphatidylcholine (DPPC), cholesterol, and diphytanoylphosphatidyl choline (DPhPC), DPIDA selectively partitioned into the more ordered phases, either solid or liquid-ordered (L(o)) depending on membrane composition. Fluorescence imaging established the phase behavior of the resulting quaternary lipid system. Fluorescence correlation spectroscopy confirmed the fluidity of the L(o) phase containing DPIDA. In the presence of CuCl(2), the iminodiacetic acid (IDA) headgroup of DPIDA forms the Cu(II)-IDA complex that exhibits a high affinity for histidine residues. His-tagged proteins were bound specifically to domains enriched in DPIDA, demonstrating the capacity to target protein binding selectively to both solid and L(o) phases. Steric pressure from the crowding of surface-bound proteins transformed the domains into tubules with persistence lengths that depended on the phase state of the lipid domains.
authors.affiliation: Sandia National Laboratories, Livermore, California 94551, USA.
authors.forename: Jeanne C
authors.initials: JC
authors.lastname: Stachowiak
authors.forename: Carl C
authors.initials: CC
authors.lastname: Hayden
authors.forename: Mari Angelica A
authors.initials: MA
authors.lastname: Sanchez
authors.forename: Julia
authors.initials: J
authors.lastname: Wang
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Bunker
authors.forename: James A
authors.initials: JA
authors.lastname: Voigt
authors.forename: Darryl Y
authors.initials: DY
authors.lastname: Sasaki
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D008956:Models, Chemical; D010713:Phosphatidylcholines / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D053835:Unilamellar Liposomes / Q000737:chemistry*
chemical_list: D010713:Phosphatidylcholines; D011506:Proteins; D053835:Unilamellar Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; C021016:1,2-diphytanoylphosphatidylcholine; D002784:Cholesterol