scholarly journals Phospholipid membranes promote the early stage assembly of α-synuclein aggregates

2018 ◽  
Author(s):  
Zhengjian Lv ◽  
Mohtadin Hashemi ◽  
Siddhartha Banerjee ◽  
Karen Zagorski ◽  
Jean-Christophe Rochet ◽  
...  

AbstractDevelopment of Parkinson’s disease is associated with spontaneous self-assembly of α-synuclein (α-syn). Efforts aimed at understanding this process have produced little clarity and the mechanism remains elusive. We report a novel effect of phospholipid bilayers on the catalysis of α-syn aggregation from monomers. We directly visualized α-syn aggregation on supported lipid bilayers using time-lapse atomic force microscopy. We discovered that α-syn assemble in aggregates on bilayer surfaces even at the nanomolar concentration of monomers in solution. The efficiency of the aggregation process depends on the membrane composition, being highest for a negatively charged bilayer. Furthermore, assembled aggregates can dissociate from the surface, suggesting that on-surface aggregation can be a mechanism by which pathological aggregates are produced. Computational modeling revealed that interaction of α-syn with bilayer surface changes the protein conformation and its affinity to assemble into dimers, and these properties depend on the bilayer composition. A model of the membrane-mediated aggregation triggering the assembly of neurotoxic aggregates is proposed.

2014 ◽  
Vol 5 ◽  
pp. 26-35 ◽  
Author(s):  
Tian Tian ◽  
Burapol Singhana ◽  
Lauren E Englade-Franklin ◽  
Xianglin Zhai ◽  
T Randall Lee ◽  
...  

The solution self-assembly of multidentate organothiols onto Au(111) was studied in situ using scanning probe nanolithography and time-lapse atomic force microscopy (AFM). Self-assembled monolayers (SAMs) prepared from dilute solutions of multidentate thiols were found to assemble slowly, requiring more than six hours to generate films. A clean gold substrate was first imaged in ethanolic media using liquid AFM. Next, a 0.01 mM solution of multidentate thiol was injected into the liquid cell. As time progressed, molecular-level details of the surface changes at different time intervals were captured by successive AFM images. Scanning probe based nanofabrication was accomplished using protocols of nanografting and nanoshaving with n-alkanethiols and a tridentate molecule, 1,1,1-tris(mercaptomethyl)heptadecane (TMMH). Nanografted patterns of TMMH could be inscribed within n-alkanethiol SAMs; however, the molecular packing of the nanopatterns was less homogeneous compared to nanopatterns produced with monothiolates. The multidentate molecules have a more complex assembly pathway than monothiol counterparts, mediated by sequential steps of forming S–Au bonds to the substrate.


2020 ◽  
Author(s):  
Fabio Perissinotto ◽  
Valeria Rondelli ◽  
Beatrice Senigagliesi ◽  
Paola Brocca ◽  
László Almásy ◽  
...  

AbstractExtracellular vesicles (EVs) represent a potent intercellular communication system. Within a lipid bilayer such small vesicles transport biomolecules between cells and throughout the body, strongly influencing the fate of recipient cells. Due to their specific biological functions they have been proposed as biomarkers for various diseases and as optimal candidates for therapeutic applications. Despite of their extreme biological relevance, the small size (30 to a few hundred nanometers in diameter) of EVs still poses a great challenge for their isolation, quantification and biophysical/biochemical characterization, therefore the complex network of EVs and cells as well as their interaction remains to be further revealed. Here we propose a multiscale platform based on Atomic Force Microscopy, Small Angle X-ray Scattering, Small Angle Neutron Scattering and Neutron Reflectometry to reveal structure-function correlations of purified EVs through the analysis of their interaction with model membrane systems, in form of both supported lipid bilayers and suspended unilamellar vesicles of variably complex composition. The analysis reveals a strong interaction of EVs with the model membranes and preferentially with liquid ordered raft-like lipid domains, and opens the way to understand uptake mechanisms in different vesicle to cell membrane relative compositions.


2010 ◽  
Vol 82 (4) ◽  
Author(s):  
Chinmay Das ◽  
Khizar H. Sheikh ◽  
Peter D. Olmsted ◽  
Simon D. Connell

2015 ◽  
Vol 108 (2) ◽  
pp. 168a
Author(s):  
Raghavendar Reddy Sanganna Gari ◽  
Nathan Frey ◽  
Brendan Marsh ◽  
Chunfeng Mao ◽  
Linda Randall ◽  
...  

Author(s):  
Zhengjian Lv ◽  
Siddhartha Banerjee ◽  
Karen Zagorski ◽  
Yuri L. Lyubchenko

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