Highlighting the effect of amyloid beta assemblies on the mechanical properties and conformational stability of cell membrane

Alzheimer disease (AD) is the most common cause of dementia, characterized by a progressive decline in cognitive function due to the abnormal aggregation and deposition of Amyloid beta (Aβ) fibrils in the brain of patients. In this context, the molecular mechanisms of protein misfolding and aggregation that are known to induce significant biophysical alterations in cells, including destabilization of plasma membranes, remain partially unclear. Physical interaction between the Aβ assemblies and the membrane leads to the disruption of the cell membrane in multiple ways including, surface carpeting, generation of transmembrane channels and detergent-like membrane dissolution. Understanding the impact of amyloidogenic protein in different stages of aggregation with the plasma membrane, plays a crucial role to fully elucidate the pathological mechanisms of AD. Within this framework, computer simulations represent a powerful tool able to shed lights on the interactions governing the structural influence of Aβ proteins on biological membrane. In this study, molecular dynamics (MD) simulations have been performed in order to characterize how POPC bilayer conformational and mechanical properties are affected by the interaction with Aβ11-42 peptide, oligomer and fibril.