title: The interaction of polyphenols with bilayers: conditions for increasing bilayer adhesion.
abstract: Because proteins and other molecules with a high polyphenol content are commonly involved in adhesion processes, we are investigating the interactions between polyphenols and biological materials. A naturally occurring polyphenol that binds a variety of proteins and lipids is tannic acid (TA), which contains five digallic acid residues covalently linked to a central D-glucose. A previous study has shown that TA increases the adhesion between apposing phosphatidylcholine (PC) bilayers and over a very narrow concentration range collapses the interbilayer fluid space from about 15 A to 5 A. To determine the chemical requirements a polyphenolic molecule must possess to increase bilayer adhesion, we have synthesized several simpler TA analogs that vary in their size, shape, and number of gallic acid and hydroxyl groups. X-ray diffraction, absorbance, binding, and differential scanning calorimetry measurements were used to investigate the interaction of these polyphenolic molecules with egg PC (EPC) and dipalmitoyl PC (DPPC) bilayers. Of these synthetic polyphenols, only penta-O-galloyl-alpha-D-glucose (PGG) was able to completely mimic the effects of TA by collapsing the interbilayer fluid space from 15 A to 5 A, decreasing the dipole potential by about 300 mV, increasing the transition enthalpy of DPPC liposomes, and inducing an interdigitated phase in DPPC. Binding studies indicated that the fluid space was reduced to 5 A at an EPC:PGG mole ratio of 5:1. We conclude that these polyphenols collapse the fluid space of PC bilayers because they 1) are amphipathic and partition into the bilayers interfacial region, 2) are long enough to span the interbilayer space, 3) contain several gallic acids distributed so that they can partition simultaneously into apposing bilayers, and 4) have sufficient gallic acid residues to interact with all lipid headgroups and cover the bilayer surface. Under these conditions we conclude that the polyphenols from interbilayer bridges. We argue that these bridges are stabilized by increased adhesion arising from an increased van der Waals interaction between apposing bilayers, electrostatic interactions between the pi electrons in the phenol ring and the -(N+CH3)3 groups on the PC headgroups, decreased hydration repulsion between bilayers, and hydrogen bonds between the H-bond-donating moieties on the polyphenols and H-bond-accepting groups in the bilayer.
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: N W
authors.initials: NW
authors.lastname: Huh
authors.forename: N A
authors.initials: NA
authors.lastname: Porter
authors.forename: T J
authors.initials: TJ
authors.lastname: McIntosh
authors.forename: S A
authors.initials: SA
authors.lastname: Simon
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D001565:Benzoates; D002152:Calorimetry, Differential Scanning; D004586:Electrophoresis; D005419:Flavonoids; D005960:Glucosides; D047348:Hydrolyzable Tannins / Q000737:chemistry*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D010636:Phenols / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D059808:Polyphenols; D012997:Solvents; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D001565:Benzoates; D005419:Flavonoids; D005960:Glucosides; D047348:Hydrolyzable Tannins; D008051:Lipid Bilayers; D010636:Phenols; D010713:Phosphatidylcholines; D011108:Polymers; D059808:Polyphenols; D012997:Solvents; D015060:1,2-Dipalmitoylphosphatidylcholine