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DENDRITIC POLYMERS
Universal glue for cells
A dendritic polymer consisting of inversely oriented lipid head groups on a polyvalent polyglycerol scaold makes an eective reversible biomembrane adhesive that may nd use as a tissue sealant and a drug-delivery vehicle.
Holger Frey
Unlike conventional, linear polymer chains, hyperbranched polymers a subclass of dendritic polymers
have a tree-like, random branch-on-branch structure with a large number of end groups and an overall globular shape1,2.
Such a structure makes dendritic polymers amenable to multiple functionalization. Taking advantage of this, DonaldBrooks, JayachandranKizhakkedathu and colleagues report in NatureMaterials that dendritic polymers can be synthesized to displayan unexpected function: biomembrane adhesion3. The authors show that hyperbranched polyglycerols decorated with multiple choline phosphate (CP) groups which possess the inverse orientation of phosphatidyl choline (PC), the end groupof the major lipid present in eukaryotic cell membranes show a strong affinity for biological membranes, and thereby exhibit great potential for a number of biomedical
applications, such as tissue sealing and drug delivery.
Since their introduction in 19994,
hyperbranched polyglycerols have found multiple uses, for instance in bioconjugation, surface modication and metalnanoparticle stabilization5,6.
As aliphatic polyethers, polyglycerols resemble, both in chemical structure and excellent biocompatibility, the widelyused linear molecule poly(ethylene glycol) (PEG) the gold standard polymer in pharmaceutics and medicine. However, both PEG and polyglycerol have low capacity to bind to cell membranes, yet polyglycerols oer a larger number of end groups available for functionalization.
Brooks and co-authors attached multiple CP groups at the termini of the polyether scaolds through the efficient azidealkyne click chemistry7 (Fig.1a). In particular,the researchers systematically varied the
concentration of CPs attached to two hyperbranched-polyglycerol samples of dierent molecular weights (23 and 65kDa). They observed that, surprisingly, these multivalent dendritic structures strongly bound to human red blood cells in particular, as many as 2.5105 moleculesof 65kDa polyglycerol terminated with 80 CP groups bound to each cell in a solution of ~10mgml1 of the polymer and that the cells formed aggregates when they were exposed to a saline-buer solution with CP-terminated polymers (Fig.1b). Instead, PC-decorated polyglycerols bound to the cells only weakly (1.8104molecules under roughly the same conditions). Also, a comparison of molecular weights revealed stronger binding for the 23kDa constructs, which is at odds with what is expected...