Surfactant Micelles

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Last Updated: Thursday, 18 February 2021 09:40

micelles

The Martini force field is ideally suited to study formation of micelles, especially because it allows long simulation times required for the equilibration of surfactant solutions. Still, the ability to obtain an equilibrated micellar size distribution depends on the type of surfactant - exchange of surfactants between micelles, and fusion and fission of small micelles is only observed for surfactants with a relative high CMC. For instance, relatively long tail surfactants such as DPC (dodecyl-phosphatidylcholine) can be observed to self-assemble into micelles, but convergence of the size distribution is very slow [1]. Recent Martini simulations studies on less hydrophobic surfactants, including acyl-trimethylammonium chloride [2,4], SDS [3], and C12E5 [5, see figure], however, are able to obtain equilibrium, and reveal interesting phenomena such as the sphere-to-rod transition [4,5].

In a comparative study [6] it is concluded that the Martini model can reproduce experimental CMCs and aggregation numbers for nonionic surfactants reasonably well. The temperature dependence, however, is shown to be incorrect, a known shortcoming of CG models in general. Martini simulations of micelles can also be used to provide starting sturctures for fine-grained models, as shown in a study of lyso-lipids [7], and to provide details on the absorption and desorption process of non-ionic surfactants [8].

[1]  S.J. Marrink, A.H. de Vries, A.E. Mark. Coarse grained model for semi-quantitative lipid simulations. JPC-B, 108:750-760, 2004. abstract

[2] S.V. Burov, N.P. Obrezkov, A.A. Vanin, E. M. Piotrovskaya. Molecular dynamic simulation of micellar solutions: A coarse-grain model. Colloid J. 70:1-5, 2008.

[3] S. Jalili, M. Akhavan. A coarse-grained molecular dynamics simulation of a sodium dodecyl sulfate micelle in aqueous solution. Coll. Surfaces A., 352:99-102, 2009.

[4]  A.V. Sangwai, R. Sureshkumar. Coarse-grained molecular dynamics simulations of the sphere to rod transition in surfactant micelles. Langmuir, 27:6628–663, 2011.

[5] M. Velinova, D. Sengupta, A. Tadjer, S.J. Marrink. Sphere-to-rod transitions of nonionic surfactant micelles in aqueous solution modeled by molecular dynamics simulations, Langmuir, 27:14071–14077, 2011. abstract

[6] S.A. Sanders, A.Z. Panagiotopoulos. Micellization behavior of coarse grained surfactant models. J. Chem. Phys. 132:114902, 2010.

[7] P. Brocos, P. Mendoza-Espinosa, R. Castillo, J. Mas-Oliva, A. Pineiro. Multiscale molecular dynamics simulations of micelles: coarse-grain for self-assembly and atomic resolution for finer details. Soft Matter, ASAP 2012. DOI: 10.1039/c2sm25877c

[8] Y.N. Ahn, G. Mohan, D.I. Kopelevich. Collective degrees of freedom involved in absorption and desorption of surfactant molecules in spherical non-ionic micelles. J. Chem. Phys. 137:164902, 2012.

 

 

Protofibril self-assembly

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Last Updated: Wednesday, 21 August 2013 11:44

J. Sørensen, X. Periole, K.K. Skeby, S.J. Marrink, B. Schiøtt. Protofibrillar assembly toward the formation of amyloid fibrils, J. Phys. Chem. Lett., 2:2385–2390, 2011.

The formation and growth of amyloid fibrils was investigated using coarse-grained molecular dynamics simulations. In particular, we studied the assembly of amylin(20–29) peptides, preassembled into protofibril fragments. The systems consisted of 27 protofibril fragments initially distributed onto a regular cubic grid with random orientation. Their association was followed on the μs time scale. At 300 K, it was observed that, while the assemblies formed are mainly disordered, there was an apparent preference for the fragments to associate such that an elongation of the structures predominates over their lateral extension. Increasing the temperature in the simulations resulted in an increase of the contact surfaces and allowed for rearrangement within the prefibrillar aggregates over longer time scales. The preferential elongation-like growth mechanism observed at 300 K was not persistent at higher temperatures indicative of a shift in growth pathway, congruent with experimental observations that changing growth conditions alters the morphology of the fibrils.

Membrane binding of AMPs

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Last Updated: Wednesday, 21 August 2013 11:44

"Competing interactions for antimicrobial selectivity based on charge complementarity"

Carola I.E. von Deuster, Volker Knecht.

Biochimica et Biophysica Acta (BBA) - Biomembranes, Volume 1808, Issue 12, December 2011, Pages 2867-2876

Antimicrobial peptides (AMPs) are an evolutionary conserved component of the innate immune system and possible templates for the development of new antibiotics. An important property of antimicrobial peptides is their ability to discriminate bacterial from eucaryotic cells which is attributed to the difference in lipid composition of the outer leaflet of the plasma membrane between the two types of cells. Whereas eucaryotic cells usually expose zwitterionic lipids, procaryotic cells expose also anionic lipids which bind the cationic antimicrobial peptides electrostatically. An example is the antimicrobial peptide NK-2 which is highly cationic and favors binding to anionic membranes. In the present study, the difference in binding affinity of NK-2 for palmitoyl-oleoyl-phosphatidyl-glycerol (POPG) and palmitoyl-oleoyl-phosphatidyl-choline (POPC) is studied using molecular dynamics simulations in conjunction with a coarse grained model and thermodynamic integration, by computing the change in free energy and its components upon the transfer of NK-2 from POPC to POPG. The transfer is indeed found to be highly favorable. Interestingly, the favorable contribution from the electrostatic interaction between the peptide and the anionic lipids is overcompensated by an unfavorable contribution from the change in lipid–cation interactions due to the release of counterions from the lipids. The increase in entropy due to the release of the cations is compensated by other entropic components. The largest favorable contribution arises from the solvation of the counterions. Overall the interaction between NK-2 and POPG is not determined by a single driving force but a subtle balance of competing interactions.

 

 

Crowded membranes

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Last Updated: Wednesday, 21 August 2013 11:24

Transmembrane helices can induce domain formation in crowded model membranes

Jan Domanski, Siewert J. Marrink, and Lars V. Schäfer. BBA Biomembranes, 1818:984-994, 2012. doi:10.1016/j.bbamem.2011.08.021

 
 
 
crowded
 
We studied compositionally heterogeneous multi-component model membranes comprised of saturated lipids, unsaturated lipids, cholesterol, and α-helical TM protein models using coarse-grained molecular dynamics simulations. Reducing the mismatch between the length of the saturated and unsaturated lipid tails reduced the driving force for segregation into liquid-ordered (lo) and liquid-disordered (ld) lipid domains. Cholesterol depletion had a similar effect, and binary lipid mixtures without cholesterol did not undergo large-scale phase separation under the simulation conditions. The phase-separating ternary dipalmitoyl-phosphatidylcholine (DPPC)/dilinoleoyl-PC (DLiPC)/cholesterol bilayer was found to segregate into lo and ld domains also in the presence of a high concentration of ΤΜ helices. The ld domain was highly crowded with TM helices (protein-to-lipid ratio ~ 1:5), slowing down lateral diffusion by a factor of 5–10 as compared to the dilute case, with anomalous (sub)-diffusion on the μs time scale. The membrane with the less strongly unsaturated palmitoyl-linoleoyl-PC instead of DLiPC, which in the absence of TM α-helices less strongly deviated from ideal mixing, could be brought closer to a miscibility critical point by introducing a high concentration of TM helices. Finally, the 7-TM protein bacteriorhodopsin was found to partition into the ld domains, irrespective of hydrophobic matching. These results show that it is possible to directly study the lateral reorganization of lipids and proteins in compositionally heterogeneous and crowded model biomembranes with coarse-grained molecular dynamics simulations, a step toward simulations of realistic, compositionally complex cellular membranes. This article is part of a Special Issue entitled: Protein Folding in Membranes.

Amphipols

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Last Updated: Wednesday, 21 August 2013 11:17

All-Atom and Coarse-Grained Molecular Dynamics Simulations of a Membrane Protein Stabilizing Polymer

Jason D Perlmutter , William J Drasler , Wangshen Xie , Jiali Gao , Jean-Luc Popot , and Jonathan Sachs. Langmuir, Just Accepted, 2011. DOI: 10.1021/la202103v

 
 
 
Amphipathic polymers called amphipols (APols) have been developed as an alternative to detergents for stabilizing membrane proteins (MPs) in aqueous solutions. APols provide MPs with a particularly mild environment and, as a rule, keep them in a native and functional state for longer periods than detergents do. Amphipol A8-35, a derivative of polyacrylate, is widely used and has been particularly well studied experimentally. In aqueous solutions, A8-35 molecules self-assemble into well-defined globular particles, with a mass of ~40 kDa and a Rg of ~2.4 nm. As a first step towards describing MP/A8-35 complexes by molecular dynamics (MD), we present three sets of simulations of the pure APol particle. First, we performed a series of all-atom MD (AAMD) simulations of the particle in solution, starting from an arbitrary initial configuration. While AAMD simulations result in cohesive and stable particles over a 45-ns simulation, the equilibration of the particle organization is limited. This motivated the use of coarse-grained MD (CGMD), allowing us to investigate processes on the microsecond timescale, including de novo particle assembly. We present a detailed description of the parametrization of the CGMD model from the AAMD simulations, and a characterization of the resulting CGMD particles. Our third set of simulations utilizes reverse coarse-graining (rCG), through which we obtain all-atom coordinates from a CGMD simulation. This allows higher-resolution characterization of a configuration determined by a long-timescale simulation. An excellent agreement is observed between MD models and experimental, small angle neutron scattering data. The MD data provides new insights into the structure and dynamics of A8-35 particles, possibly relevant to the stabilizing effects of APols on MPs, as well as a starting point for modeling MP/A8-35 complexes.

Fusion review

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Last Updated: Wednesday, 21 August 2013 11:24

A.J. Markvoort, S.J. Marrink. Lipid acrobatics in the membrane fusion arena, Curr. Top. Membr. 68:259-294, 2011. abstract, reprint

In this review, we describe the recent contribution of computer simulation approaches to unravel the molecular details of membrane fusion. Over the past decade, fusion between apposed membranes and vesicles has been studied using a large variety of simulation methods and systems. Despite the variety in techniques, some generic fusion pathways emerge that predict a more complex picture beyond the traditional stalk–pore pathway. Indeed the traditional pathway is confirmed in particle-based simulations, but in addition alternative pathways are observed in which stalks expand linearly rather than radially, leading to inverted-micellar or asymmetric hemifusion intermediates. Simulations also suggest that the first barrier to fusion is not the formation of the stalk, but rather, the formation of a lipid bridge consisting of one or two lipids only. Fusion occurring during the fission process involves other intermediates, however, and is not just fusion reversed. Finally, recent progress in simulations of peptide and protein-mediated fusion shows how fusion proceeds in a more biologically relevant scenario.