Thermal Reversal of Polyvalent Choline Phosphate, a Multivalent Universal Biomembrane Adhesive

Multivalent macromolecular associations are widely observed in biological systems and are increasingly being utilized in bioengineering, nanomedicine, and biomaterial applications. Control over such associations usually demands an ability to reverse the multivalent binding. While in principle this can be done with binding site competitive inhibitors, dissociation is difficult in practice due to limited site accessibility when the macromolecule is bound. We demonstrate here efficient binding reversal of multivalent linear copolymers that adhere to any mammalian cell via the universal mechanism based on choline phosphate (CP) groups binding to phosphatidyl choline (PC)-containing biomembranes. Using a smart linear polymer exhibiting a lower critical solution temperature (LCST), we take advantage of the thermal contraction of the polymer above the LCST, which reduces accessibility of the CP groups to cell membrane PC lipids. The polymer construct can then desorb from the cell surface, reversing all effects of multivalent polymer adhesion on the cell.