Effect of Amyloid-β Monomers on Lipid Membrane Mechanical Parameters–Potential Implications for Mechanically Driven Neurodegeneration in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease that results in memory loss and the impairment of cognitive skills. Several mechanisms of AD’s pathogenesis were proposed, such as the progressive accumulation of amyloid-β (Aβ) and τ pathology. Nevertheless, the exact neurodegenerative mechanism of the Aβ remains complex and not fully understood. This paper proposes an alternative hypothesis of the mechanism based on maintaining the neuron membrane’s mechanical balance. The incorporation of Aβ decreases the lipid membrane’s elastic properties, which eventually leads to the impairment of membrane clustering, disruption of mechanical wave propagation, and change in gamma oscillations. The first two disrupt the neuron’s ability to function correctly while the last one decreases sensory encoding and perception enabling. To begin discussing this mechanical-balance hypothesis, we measured the effect of two selected peptides, Aβ-40 and Aβ-42, as well as their fluorescently labeled modification, on membrane mechanical properties. The decrease of bending rigidity, consistent for all investigated peptides, was observed using molecular dynamic studies and experimental flicker-noise techniques. Additionally, wave propagation was investigated with molecular dynamic studies in membranes with and without incorporated neurodegenerative peptides. A change in membrane behavior was observed in the membrane system with incorporated Aβ.

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

“…The lack of O 2 transport to tissues explains straightforwardly how a nominally respiratory disease also leads to the dysfunction of organs such as the kidney [184,185], PoTS ( postural tachycardia syndrome [186]), myalgia in skeletal muscle [187,188], neurological disorders [189], and lactic acidosis [190,191] (the mass of lactate is too low to have been detected in our own COVID untargeted metabolomics experiments [192]), and potentially the benefits of hyperbaric O 2 therapy [193]. It is also worth stressing that amyloid structures themselves tend to be cytotoxic, often via membrane disruption [194][195][196][197][198].…”

A Systematic Approach: Molecular Dynamics Study and Parametrisation of Gemini Type Cationic Surfactants

“…Finally, data from both geometry and a Hessian matrix were used for parametrisation of modelled particles and the force fields creation. This approach was successfully used beforehand to create force fields for various particles [18,50,51]. In Supporting Materials (SM) we have delivered the detailed base of modelled 250 particles (see Microsoft Excel datasheet) with optimised force fields (see included zip file).…”

Scoping review and interpretation of myofascial pain/fibromyalgia syndrome: An attempt to assemble a medical puzzle

“…When synaptic neuromuscular activity is maintained over time, an aggregated form of amyloid beta is seen to interfere with Ach release ex vivo [251]. One adopting this biological ethos might want to examine if amyloid beta is linked to "fascial armoring", because studies suggest amyloid beta, like the cytoskeletal protein tau, is affected by or compensates for, mechanical stress [252][253][254][255][256].…”