Spontaneous Refolding of Amyloid Fibrils from One Polymorph to Another Caused by Changes in Environmental Hydrophobicity

Abstract

Here, we report a new phenomenon in which lysozyme fibrils formed in a solution of acetic acid spontaneously refold to a different polymorph through a disassembled intermediate upon the removal of acetic acid. The structural changes were revealed and characterized by deep-UV resonance Raman spectroscopy, nonresonance Raman spectroscopy, intrinsic tryptophan fluorescence spectroscopy, and atomic force microscopy. A PPII-like structure with highly solvent-exposed tryptophan residues predominates the intermediate aggregates before refolding to polymorph II fibrils. Furthermore, the disulfide (SS) bonds undergo significant rearrangements upon the removal of acetic acid from the lysozyme fibril environment. The main SS bond conformation changes from gauche–gauche–trans in polymorph I to gauche–gauche–gauche in polymorph II. Changing the hydrophobicity of the fibril environment was concluded to be the decisive factor causing the spontaneous refolding of lysozyme fibrils from one polymorph to another upon the removal of acetic acid. Potential biological implications of the discovered phenomenon are discussed.

Kinetic control in amyloid polymorphism: Different agitation and solution conditions promote distinct amyloid polymorphs of alpha-synuclein

“…A fibril polymorph may not be the final state and changing its physico-chemical environment can help it overcome the kinetic barrier to adopt an alternate conformation. In recent work, such an observation was reported for in vitro generated lysozyme fibrils, wherein two polymorphs were interconvertible with a change in hydrophobicity of the buffer solution [71].…”

Kinetic control in amyloid polymorphism: Different agitation and solution conditions promote distinct amyloid polymorphs of alpha-synuclein

“…A fibril polymorph may not be the final state and changing its physico-chemical environment can help it overcome the kinetic barrier to adopt an alternate conformation. In recent work, such an observation was reported for in vitro generated lysozyme fibrils, wherein two polymorphs were interconvertible with a change in hydrophobicity of the buffer solution [71]. Polymorph interconversion is usually a rare phenomenon because for such interconversion to occur, the stable, rigid amyloid core must disassemble before reassembling, which is a kinetically unfeasible process.…”