Entropic elasticity based coarse-grained model of lipid membranes

2018 ◽  
Vol 148 (16) ◽  
pp. 164705 ◽  
Author(s):  
Shuo Feng ◽  
Yucai Hu ◽  
Haiyi Liang
Keyword(s):  
Lipid Membranes ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Entropic Elasticity

scholarly journals Physical mechanisms of amyloid nucleation on fluid membranes

2020 ◽  
Vol 117 (52) ◽  
pp. 33090-33098
Author(s):  
Johannes Krausser ◽  
Tuomas P. J. Knowles ◽  
Anđela Šarić
Keyword(s):  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
Amyloid Fibrils ◽  
Lipid Membrane ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Physical Mechanisms ◽  
Fluid Membranes ◽  
Protein Membrane ◽  
Protein Rich

Biological membranes can dramatically accelerate the aggregation of normally soluble protein molecules into amyloid fibrils and alter the fibril morphologies, yet the molecular mechanisms through which this accelerated nucleation takes place are not yet understood. Here, we develop a coarse-grained model to systematically explore the effect that the structural properties of the lipid membrane and the nature of protein–membrane interactions have on the nucleation rates of amyloid fibrils. We identify two physically distinct nucleation pathways—protein-rich and lipid-rich—and quantify how the membrane fluidity and protein–membrane affinity control the relative importance of those molecular pathways. We find that the membrane’s susceptibility to reshaping and being incorporated into the fibrillar aggregates is a key determinant of its ability to promote protein aggregation. We then characterize the rates and the free-energy profile associated with this heterogeneous nucleation process, in which the surface itself participates in the aggregate structure. Finally, we compare quantitatively our data to experiments on membrane-catalyzed amyloid aggregation of α-synuclein, a protein implicated in Parkinson’s disease that predominately nucleates on membranes. More generally, our results provide a framework for understanding macromolecular aggregation on lipid membranes in a broad biological and biotechnological context.

Structural and dynamic properties of different DPPC lipid membranes using a coarse-grained model

2017 ◽  
Vol 259 ◽  
pp. e10
Author(s):  
Bei Li ◽  
Yuan Cheng ◽  
Jingjie Yeo ◽  
Narayanaswamy Sridhar ◽  
Yongwei Zhang
Keyword(s):  
Lipid Membranes ◽  
Dynamic Properties ◽  
Coarse Grained ◽  
Coarse Grained Model

scholarly journals Physical mechanisms of amyloid nucleation on fluid membranes

2019 ◽  
Author(s):  
Johannes Krausser ◽  
Tuomas P. J. Knowles ◽  
Anđela Šarić
Keyword(s):  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
Amyloid Fibrils ◽  
Lipid Membrane ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Physical Mechanisms ◽  
Membrane Affinity ◽  
Fluid Membranes ◽  
Protein Membrane

Biological membranes can dramatically accelerate the aggregation of normally soluble protein molecules into amyloid fibrils and alter the fibril morphologies, yet the molecular mechanisms through which this accelerated nucleation takes place are not yet understood. Here, we develop a coarse-grained model to systematically explore the effect that the structural properties of the lipid membrane and the nature of protein-membrane interactions have on the nucleation rates of amyloid fibrils. We identify two physically distinct nucleation pathways and quantify how the membrane fluidity and protein-membrane affinity control the relative importance of those molecular pathways. We find that the membrane’s susceptibility to reshaping and being incorporated into the fibrillar aggregates is a key determinant of its ability to promote protein aggregation. We then characterise the rates and the free energy profile associated to this heterogeneous nucleation process in which the surface itself participates in the aggregate structure. Finally, we compare quantitatively our data to experiments on membrane-catalysed amyloid aggregation of α-synuclein, a protein implicated in Parkinson’s disease that predominately nucleates on membranes. More generally, our results provide a framework for understanding macromolecular aggregation on lipid membranes in a broad biological and biotechnological context.

Insights Into Crowding Effects on Protein Stability From a Coarse-Grained Model

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Vincent K. Shen ◽  
Jason K. Cheung ◽  
Jeffrey R. Errington ◽  
Thomas M. Truskett
Keyword(s):  
Protein Stability ◽  
Coarse Grained ◽  
Protein Solutions ◽  
Native State ◽  
High Concentration ◽  
Coarse Grained Model ◽  
Excluded Volume Effects ◽  
Thermodynamic Phase ◽  
Broad Interest ◽  
Liquid Liquid Phase Separation

Proteins aggregate and precipitate from high concentration solutions in a wide variety of problems of natural and technological interest. Consequently, there is a broad interest in developing new ways to model the thermodynamic and kinetic aspects of protein stability in these crowded cellular or solution environments. We use a coarse-grained modeling approach to study the effects of different crowding agents on the conformational equilibria of proteins and the thermodynamic phase behavior of their solutions. At low to moderate protein concentrations, we find that crowding species can either stabilize or destabilize the native state, depending on the strength of their attractive interaction with the proteins. At high protein concentrations, crowders tend to stabilize the native state due to excluded volume effects, irrespective of the strength of the crowder-protein attraction. Crowding agents reduce the tendency of protein solutions to undergo a liquid-liquid phase separation driven by strong protein-protein attractions. The aforementioned equilibrium trends represent, to our knowledge, the first simulation predictions for how the properties of crowding species impact the global thermodynamic stability of proteins and their solutions.

Sign in / Sign up

Export Citation Format

Share Document