Nucleation in gold nanoclusters

The goal of this work is to provide a detailed description of the freezing mechanism in gold clusters. This is accomplished by using constrained Monte Carlo simulations combined with parallel tempering algorithms to evaluate the free energy barriers for various temperatures with respect to crystalline order parameters on a 456 atom cluster. Our simulation results help us to challenge the usual assumption of classic nucleation theory where nucleation starts at the center of a cluster, showing instead that nucleation is favored by freezing started at the surface. We study simplistic phenomenological models for surface freezing and find that the three phase contact line free energy term must be included in order to properly describe the features of the free energy barriers. Furthermore, we propose an alternative free energy parameter with which we are able to identify a kinetic spinodal temperature where the nucleation barrier disappears and find that the critical cluster size remains finite at the limit of stability of the fluid phase. This result is supported by Molecular Dynamics simulations

Lipid-Protein Interactions Are Unique Fingerprints for Membrane Proteins

Cell membranes contain hundreds of different proteins and lipids in an asymmetric arrangement. Our current understanding of the detailed organization of cell membranes remains rather elusive, because of the challenge to study fluctuating nanoscale assemblies of lipids and proteins with the required spatiotemporal resolution. Here, we use molecular dynamics simulations to characterize the lipid environment of 10 different membrane proteins. To provide a realistic lipid environment, the proteins are embedded in a model plasma membrane, where more than 60 lipid species are represented, asymmetrically distributed between the leaflets. The simulations detail how each protein modulates its local lipid environment in a unique way, through enrichment or depletion of specific lipid components, resulting in thickness and curvature gradients. Our results provide a molecular glimpse of the complexity of lipid-protein interactions, with potentially far-reaching implications for our understanding of the overall organization of real cell membranes

Role of the Influenza M2 Protein on Viral Budding and Scission

The budding of enveloped viruses is a complex multi-step process requiring alterations in membrane curvature and scission at the neck of the budding virion. M2 is a pH-dependent matrix protein from influenza virus widely known for its role in viral uncoating and the target of the amantadine flu drug that prevents proton transport. An additional role played by M2 relies on collective effects where M2 clusters have been hypothesized to induce local membrane curvature, resulting in a reduced energetic cost associated with the bending of the membrane and where the budding of virus particles takes place in a cholesterol-dependent manner (Rossman et al., Cell 142, pp. 902-913, 2010). The additional M2 role is striking in that many viruses utilize host endosomal sorting complex (ESCRT) proteins for virus budding. However, it was found that the mechanism for influenza can be ESCRT-independent. MD simulations (MD) were used to study the behavior of Influenza M2 proteins at various aggregation conditions and embedded in model lipid membranes. The study of this protein presented a unique challenge in that it has a dual role, and epitomizes a frontier of problems in biology where proteins have additional, unsuspected roles, and require a combination of techniques to uncover their function. Our general philosophy to tackle the aggregation of proteins at the mesoscopic level, consists in first, the combination of atomistic-level molecular simulation techniques to investigate the details of molecular interactions. Coarse-grained simulations are then used to extract free energies between protein pairs mediated by lipids. The calculation of membrane induced fingerprints enabled us to propose a scheme that may be used to study membrane induced curvature via cooperative interactions from multiple proteins whether these belong to the same kind or in combination with any other transmembrane protein types. The approach taken is relevant because the calculation of the energetics of membrane topology transformations is beyond the realm of possibility for standard molecular dynamics simulations

The Mechanism of Collapse of Heterogeneous Lipid Monolayers

AbstractCollapse of homogeneous lipid monolayers is known to proceed via wrinkling/buckling, followed by folding into bilayers in water. For heterogeneous monolayers with phase coexistence, the mechanism of collapse remains unclear. Here, we investigated collapse of lipid monolayers with coexisting liquid-liquid and liquid-solid domains using molecular dynamics simulations. The MARTINI coarse-grained model was employed to simulate monolayers of ∼80 nm in lateral dimension for 10–25 μs. The monolayer minimum surface tension decreased in the presence of solid domains, especially if they percolated. Liquid-ordered domains facilitated monolayer collapse due to the spontaneous curvature induced at a high cholesterol concentration. Upon collapse, bilayer folds formed in the liquid (disordered) phase; curved domains shifted the nucleation sites toward the phase boundary. The liquid (disordered) phase was preferentially transferred into bilayers, in agreement with the squeeze-out hypothesis. As a result, the composition and phase distribution were altered in the monolayer in equilibrium with bilayers compared to a flat monolayer at the same surface tension. The composition and phase behavior of the bilayers depended on the degree of monolayer compression. The monolayer-bilayer connection region was enriched in unsaturated lipids. Percolation of solid domains slowed down monolayer collapse by several orders of magnitude. These results are important for understanding the mechanism of two-to-three-dimensional transformations in heterogeneous thin films and the role of lateral organization in biological membranes. The study is directly relevant for the function of lung surfactant, and can explain the role of nanodomains in its surface activity and inhibition by an increased cholesterol concentration