Polyvalent choline phosphate as a universal biomembrane adhesive

Abstract

Phospholipids in the cell membranes of all eukaryotic cells contain phosphatidyl choline (PC) as the headgroup. Here we show that hyperbranched polyglycerols (HPGs) decorated with the 'PC-inverse' choline phosphate (CP) in a polyvalent fashion can electrostatically bind to a variety of cell membranes and to PC-containing liposomes, the binding strength depending on the number density of CP groups per macromolecule. We also show that HPG-CPs can cause cells to adhere with varying affinity to other cells, and that binding can be reversed by subsequent exposure to low molecular weight HPGs carrying small numbers of PCs. Moreover, PC-rich membranes adsorb and rapidly internalize fluorescent HPG-CP but not HPG-PC molecules, which suggests that HPG-CPs could be used as drug-delivery agents. CP-decorated polymers should find broad use, for instance as tissue sealants and in the self-assembly of lipid nanostructures.

Structures and Synthesis of Zwitterionic Polymers

“…The problem of incomplete conversion unbalancing the charge neutrality of polyzwitterions in post-polymerization modifications can in principle be avoided when reacting the precursor polymer with prefabricated zwitterionic reagents ( Figure 11) [193,[411][412][413][414][415][416][417][418]. Still, this implies the judicious choice of the reactive groups used for the modification.…”

“…If one of these functional groups is fixed on the precursor polymer and the other one to the zwitterionic reagent, this coupling strategy holds both the potential for high coupling efficiencies and selectivities as well as (for charge neutrality) harmless residual reactive sites if remaining. So far, the use of zwitterionic alkynes has been preferred, which are coupled to polymeric azides ( Figure 12) [193,[414][415][416][417][418]. Still, the inverse strategy should be equally feasible.…”

Choline Phosphate Functionalized Cellulose Membrane Developed as Potential Hemostasis Dressing Based on a Unique Bioadhesion Mechanism

“…The synthesis of p-CP and p-PC followed the recently reported method [6]. Briefly, for p-CP, double-distilled dimethylamino 2-propyne (25 g, 0.3 mol), fresh anhydrous methanol (3.5 g, 0.11 mol) and anhydrous acetonitrile (60 mL) were added by turning into a thoroughly flame dried Schlenk flask protected by Argon, and cooled to -40 o C with dry ice/acetone solution.…”

“…In the present work, a choline phosphate modified cellulose membrane was developed and can be potentially used as an absorptive wound dressing in the future. In our previous work [6], we described the discovery of a universal bioadhesion mechanism based on the interaction between the head group of phosphatidyl choline (PC)-lipids and the mirror image structure, choline O-phosphate (CP). We found in fact that decorating a dendritic polymer, hyperbranched polygylcerol (HPG), with CP groups produces strong binding of the polymer construct to cell surfaces.…”

Hyperbranched aliphatic polyether polyols

“…The authors also showed that PC-rich membranes adsorb and rapidly internalize fluorescent hbPG-CPs, which paves the way to a potential use as drug-delivery agents. 197 Dendritic core-double-shell architectures consisting of a hyperbranched polyglycerol core, a long aliphatic hydrophobic inner shell, and hyperbranched polyglycerol-based hydrophilic outer shell have been synthesized by Burakowska and Haag. 198 This unique architecture was inspired by the molecular mimicry of a liposome.…”