Emppu Salonen

BODIPY-cholesterol: a new tool to visualize sterol trafficking in living cells and organisms.

Analysis of sterol distribution and transport in living cells has been hampered by the lack of bright, photostable fluorescent sterol derivatives that closely resemble cholesterol. In this study, we employed atomistic simulations and experiments to characterize a cholesterol compound with fluorescent boron dipyrromethene difluoride linked to sterol carbon‐24 (BODIPY‐cholesterol). This probe packed in the membrane and behaved similarly to cholesterol both in normal and in cholesterol‐storage disease cells and with trace amounts allowed the visualization of sterol movement in living systems. Upon injection into the yolk sac, BODIPY‐cholesterol did not disturb zebrafish development and was targeted to sterol‐enriched brain regions in live fish. We conclude that this new probe closely mimics the membrane partitioning and trafficking of cholesterol and, because of its excellent fluorescent properties, enables the direct monitoring of sterol movement by time‐lapse imaging using trace amounts of the probe. This is, to our knowledge, the first cholesterol probe that fulfills these prerequisites.

Analytical interatomic potential for modeling nonequilibrium processes in the W-C-H system

A reactive interatomic potential based on an analytical bond-order scheme is developed for the ternary system W–C–H. The model combines Brenner’s hydrocarbon potential with parameter sets for W–W, W–C, and W–H interactions and is adjusted to materials properties of reference structures with different local atomic coordinations including tungsten carbide, W–H molecules, as well as H dissolved in bulk W. The potential has been tested in various scenarios, such as surface, defect, and melting properties, none of which were considered in the fitting. The intended area of application is simulations of hydrogen and hydrocarbon interactions with tungsten, which have a crucial role in fusion reactor plasma-wall interactions. Furthermore, this study shows that the angular-dependent bond-order scheme can be extended to second nearest-neighbor interactions, which are relevant in body-centered-cubic metals. Moreover, it provides a possibly general route for modeling metal carbides.

Effects of carbon nanoparticles on lipid membranes: a molecular simulation perspective

We review recent simulation studies of carbon nanoparticles interacting with lipid membranes. We first consider the state-of-the-art methodology associated with atomistic as well as coarse-grained models of carbon nanoparticles and lipid systems, and then discuss recent simulation studies of fullerenes, carbon nanotubes and other carbon-based nanoparticles interacting with biological lipid interfaces. We close this article with a brief consideration of the future challenges guided by experiments.

Ion-irradiation-induced defects in bundles of carbon nanotubes

Abstract We study the structure and formation yields of atomic-scale defects produced by low-dose Ar ion irradiation in bundles of single-wall carbon nanotubes. For this, we employ empirical potential molecular dynamics and simulate ion impact events over an energy range of 100–1000 eV. We show that the most common defects produced at all energies are vacancies on nanotube walls, which at low temperatures are metastable but long-lived defects. We further calculate the spatial distribution of the defects, which proved to be highly non-uniform. We also show that ion irradiation gives rise to the formations of inter-tube covalent bonds mediated by carbon recoils and nanotube lattice distortions due to dangling bond saturation. The number of inter-tube links, as well as the overall damage, linearly grows with the energy of incident ions.

Influence of Ethanol on Lipid Membranes: From Lateral Pressure Profiles to Dynamics and Partitioning.

We have combined experiments with atomic-scale molecular dynamics simulations to consider the influence of ethanol on a variety of lipid membrane properties. We first employed isothermal titration calorimetry together with the solvent-null method to study the partitioning of ethanol molecules into saturated and unsaturated membrane systems. The results show that ethanol partitioning is considerably more favorable in unsaturated bilayers, which are characterized by their more disordered nature compared to their saturated counterparts. Simulation studies at varying ethanol concentrations propose that the partitioning of ethanol depends on its concentration, implying that the partitioning is a nonideal process. To gain further insight into the permeation of alcohols and their influence on lipid dynamics, we also employed molecular dynamics simulations to quantify kinetic events associated with the permeation of alcohols across a membrane, and to characterize the rotational and lateral diffusion of lipids and alcohols in these systems. The simulation results are in agreement with available experimental data and further show that alcohols have a small but non-vanishing effect on the dynamics of lipids in a membrane. The influence of ethanol on the lateral pressure profile of a lipid bilayer is found to be prominent: ethanol reduces the tension at the membrane-water interface and reduces the peaks in the lateral pressure profile close to the membrane-water interface. The changes in the lateral pressure profile are several hundred atmospheres. This supports the hypothesis that anesthetics may act by changing the lateral pressure profile exerted on proteins embedded in membranes.

Concerted diffusion of lipids in raft-like membranes

Currently, there is no comprehensive model for the dynamics of cellular membranes. The understanding of even the basic dynamic processes, such as lateral diffusion of lipids, is still quite limited. Recent studies of one-component membrane systems have shown that instead of single-particle motions, the lateral diffusion is driven by a more complex, concerted mechanism for lipid diffusion (E. Falck et al., J. Am. Chem. Soc., 2008, 130, 44-45), where a lipid and its neighbors move in unison in terms of loosely defined clusters. In this work, we extend the previous study by considering the concerted lipid diffusion phenomena in many-component raft-like membranes. This nature of diffusion phenomena emerge in all the cases we have considered, including both atom-scale simulations of lateral diffusion within rafts and coarse-grained MARTINI simulations of diffusion in membranes characterized by coexistence of raft and non-raft domains. The data allows us to identify characteristic time scales for the concerted lipid motions, which turn out to range from hundreds of nanoseconds to several microseconds. Further, we characterize typical length scales associated with the correlated lipid diffusion patterns and find them to be about 10 nm, or even larger if weak correlations are taken into account. Finally, the concerted nature of lipid motions is also found in dissipative particle dynamics simulations of lipid membranes, clarifying the role of hydrodynamics (local momentum conservation) in membrane diffusion phenomena.

Real‐Time Translocation of Fullerene Reveals Cell Contraction

Carbon-based nanomaterials possess unique structural, mechanical, and electronic properties that are exploited in numerous applications. The fate of nanomaterials in living systems and in the environment is largely unknown, though there is a reason for concern. Here it is shown how the interaction of fullerene with natural phenolic acid induces cell contraction. This phenomenon has a general applicability to carbon-based nanomaterials interacting with natural amphiphiles. Atomistic simulations reveal that the self-assembly of C(70)-gallic acid (GA) favors aggregation. Confocal fluorescence microscopy shows that C(70)-GA complexes translocate across the membranes of HT-29 cells and enter nuclear membranes. Confocal imaging further reveals the real-time uptake of C(70)-GA and the consequent contraction of the cell membranes. This contraction is attributed to the aggregation of nanoparticles into microsized particles promoted by cell surfaces, a new physical mechanism for deciphering nanotoxicity.

Experimental and simulation studies of a real-time polymerase chain reaction in the presence of a fullerene derivative

The real-time polymerase chain reaction of the plant gene heat shock transcription factor was fully inhibited in the presence of a fullerene derivative C(60)(OH)(20) at a concentration of 4 x 10(-4) mM. This inhibition was attributed to the interaction between the nanoparticle and Taq DNA polymerase in the reaction. Atomistic molecular dynamics simulations showed a clear tendency for hydrogen bonding between C(60)(OH)(20) and both the dNTPs and ssDNA components of the polymerase chain reaction. These studies facilitate our understanding of the fate of nanoparticles in biomolecular systems, a topic of tremendous importance for addressing the biological and environmental implications of nanomaterials.

Swift chemical sputtering of covalently bonded materials

Numerous experiments have shown that low-energy H ions and neutrals can erode amorphous carbon at ion energies of 1-10 eV, where physical sputtering is impossible, but at erosion rates which are clearly higher than those caused by thermal ions. In this paper, we will first review our computer simulation work providing an atom-level mechanism for how this erosion occurs, and then present some new results for H and He bombardment of tungsten carbide and amorphous hydrogenated silicon (a-Si:H), which indicate the mechanism can be of importance in a wide range of covalently bonded materials. We also discuss how the presented mechanism relates to previously described abstraction and etching mechanisms.

Sputtering of amorphous hydrogenated carbon by hyperthermal ions as studied by tight-binding molecular dynamics

Although the mechanisms of the erosion of carbon-based materials by low-energy hydrogen ions have recently been addressed from an atomistic point of view [see e.g. Phys. Rev. B 63 (2001) 195415], it is not clear yet whether the quantum-mechanical effects are important for an adequate description of the erosion. We now study the low-energy erosion mechanisms by tight-binding molecular dynamics, which accounts for the quantum-mechanical nature of the interactions between the impinging particle and surface. We simulate the ion-assisted bond breaking in simple model systems like carbon dimers and also model sputtering from realistic hydrogenated carbon surfaces. Our simulations confirm the empirical potential results on the low-energy erosion mechanism, and help one to distinguish between the different mechanisms of the surface erosion.