A supramolecular bottle-brush approach to disassemble amyloid fibrils

We present a new strategy to disassemble amyloid fibrils consisting of a supramolecular attachment along the fibrils’ contour length of end-terminated counter charged hydrophilic polymers. We chose as a model system to work with positively charged β-lactoglobulin fibrils (pH 2), to which sulfonic acid terminated poly(ethylene glycol) (PEG) chains are ionically attached. The attachment of PEG to the β-lactoglobulin fibrils was confirmed by electrophoretic mobility measurements and small-angle neutron scattering (SANS). This complexation results in a supramolecular bottle-brush system, in which the PEG chains, attached at high grafting densities, stretch out due to excluded volume interactions. The increase in free energy resulting from this entropy loss causes the amyloid fibrils to disassemble, which in turn allows the chains to relax. The decrease in the average contour length of the fibrils was analyzed with atomic force microscopy (AFM) by varying the molecular weight and concentration of the supramolecularly attached polymer. The resulting average contour length distributions were fitted by a Boltzmann distribution law, which yielded an average energy per unit length of the amyloid fibrils. The dependence of this energy on the molecular weight (Mw) and the grafting density of the attached polymers was calculated and compared with available polymer bottle-brush theories. Both the increase in Mw and grafting density the polymer led to a decrease in average contour length. In particular, the characteristic exponent of the Mw-dependence of the energy was found to be identical (0.51) to predictions by Semenov (0.50 in Polym. Sci. Ser. A, 2007) and close to predictions by Wang and Safran (0.375 in J. Chem. Phys., 1988). The present findings demonstrate the dynamic association among amyloid fibril building blocks and offer a new appealing supramolecular route to tune their thermodynamic characteristics and their structural properties.