Lipid oxidation controls peptide self-assembly near membranes through a surface attraction mechanism

Abstract

Oxidized model membranes have differential effects on peptide fibril formation, driven by surface attraction, peptide charge and secondary structure stabilization.

Self-assembly of peptide nanomaterials at biointerfaces: molecular design and biomedical applications

“…Martin et al investigated the effect of zwitterions (POPC), anions (POPG), oxidized phospholipids (PazePC), cholesterol, and their mixtures on the self-assembly kinetics of amyloid b (1-40) peptide (Ab40). 121 Oxidation reactions can cause the exposure of anionic lipids on the membrane, which in turn promotes the assembly of peptides. Lee et al demonstrated that the association and insertion of monomeric Ab into lipid monolayers are controlled by electrostatic interactions between Ab40 and phospholipid headgroups.…”

Peptide Self‐Assembly into Amyloid Fibrils at Hard and Soft Interfaces—From Corona Formation to Membrane Activity

“…[25] Aging is often associated with defective mechanisms [231] to combat oxidative stress, which has also been shown to accelerate the aggregation of amyloidogenic proteins. [136,232] The interaction of amyloid-forming peptides with membranes has been studied bidirectionally, that is, the role of membranes was considered not only to trigger an increased peptide aggregation rate, [25,54,[233][234][235] but also as a target of amyloid peptide activity. It is unclear whether amyloid-forming peptides first initiate pathogenic processes in membranes and change their structures, or whether changes in membranes are the cause of peptide aggregation.…”

Molecular Insights into the Dynamics of Amyloid Fibril Growth: Elongation and Lateral Assembly of GNNQQNY Protofibrils

“…The process by which these seeds form is typically slow, leading to a characteristic lag phase. However, once a protofilament or protofibril has reached a critical size it can act as a template for the addition of more peptide leading to rapid elongation and the ultimate formation of mature fibrils. , Secondary pathways, such as secondary nucleation of peptide monomers on an existing (proto)-fibril and fragmentation of fibrils can lead to additional fibril formation. − The kinetics of fibril formation is highly variable and depends on a range of physicochemical parameters, including peptide concentration, , solvent, , ionic strength, pH, temperature, and the presence of surfaces, , metal ions , or lipids. − While a higher peptide concentration or temperature typically accelerate fibril formation kinetics, ,, other factors can have both accelerating and inhibiting effects depending on their impact on peptide charges (pH, ionic strength), , peptide secondary structure (solvent, lipids), ,,− or local concentration (surfaces). , …”

“…This work focused on the growth of GNNQQNY protofibrils in water at constant temperature and pH; however, physiological environments are more complex. Environmental factors such as solvent, ionic strength, pH, temperature or the presence of surfaces, metal ions and lipids have been shown to influence fibril formation and impact amyloid growth in a variety of cases. − For example, the presence of surfaces such as cell membranes can bias the secondary structure of peptide monomers and thus inhibit fibril elongation or create seed surfaces that lead to the formation of additional protofibrils . In some cases it is the presence of biomolecular condensates as result of liquid–liquid phase separation and droplet formation that appears to promote fibril formation and growth .…”

“…18−29 For example, the presence of surfaces such as cell membranes can bias the secondary structure of peptide monomers and thus inhibit fibril elongation or create seed surfaces that lead to the formation of additional protofibrils. 28 In some cases it is the presence of biomolecular condensates as result of liquid−liquid phase separation and droplet formation that appears to promote fibril formation and growth. 68 Peptide oligomers may also form amorphous aggregates instead of amyloid fibrils depending on the physicochemical environment.…”