Hendrick W. de Haan

Clusters of Superparamagnetic Iron Oxide Nanoparticles Encapsulated in a Hydrogel: A Particle Architecture Generating a Synergistic Enhancement of the T2 Relaxation

Clusters of iron oxide nanoparticles encapsulated in a pH-responsive hydrogel are synthesized and studied for their ability to alter the T(2)-relaxivity of protons. Encapsulation of the clusters with the hydrophilic coating is shown to enhance the transverse relaxation rate by up to 85% compared to clusters with no coating. With the use of pH-sensitive hydrogel, difficulties inherent in comparing particle samples are eliminated and a clear increase in relaxivity as the coating swells is demonstrated. Agreement with Monte Carlo simulations indicates that the lower diffusivity of water inside the coating and near the particle surface leads to the enhancement. This demonstration of a surface-active particle structure opens new possibilities in using similar structures for nanoparticle-based diagnostics using magnetic resonance imaging.

Modeling the separation of macromolecules: a review of current computer simulation methods.

Theory and numerical simulations play a major role in the development of improved and novel separation methods. In some cases, computer simulations predict counterintuitive effects that must be taken into account in order to properly optimize a device. In other cases, simulations allow the scientist to focus on a subset of important system parameters. Occasionally, simulations even generate entirely new separation ideas! In this article, we review the main simulation methods that are currently being used to model separation techniques of interest to the readers of Electrophoresis. In the first part of the article, we provide a brief description of the numerical models themselves, starting with molecular methods and then moving towards more efficient coarse‐grained approaches. In the second part, we briefly examine nine separation problems and some of the methods used to model them. We conclude with a short discussion of some notoriously hard‐to‐model separation problems and a description of some of the available simulation software packages.

Stiff filamentous virus translocations through solid-state nanopores

The ionic conductance through a nanometer-sized pore in a membrane changes when a biopolymer slides through it, making nanopores sensitive to single molecules in solution. Their possible use for sequencing has motivated numerous studies on how DNA, a semi-flexible polymer, translocates nanopores. Here we study voltage-driven dynamics of the stiff filamentous virus fd with experiments and simulations to investigate the basic physics of polymer translocations. We find that the electric field distribution aligns an approaching fd with the nanopore, promoting its capture, but it also pulls fd sideways against the membrane after failed translocation attempts until thermal fluctuations reorient the virus for translocation. fd is too stiff to translocate in folded configurations. It therefore translocates linearly, exhibiting a voltage-independent mobility and obeying first-passage-time statistics. Surprisingly, lengthwise Brownian motion only partially accounts for the translocation velocity fluctuations. We also observe a voltage-dependent contribution whose origin is only partially determined.

Enhancement and degradation of the R 2* relaxation rate resulting from the encapsulation of magnetic particles with hydrophilic coatings

The effects of including a hydrophilic coating around the particles are studied across a wide range of particle sizes by performing Monte Carlo simulations of protons diffusing through a system of magnetic particles. A physically realistic methodology of implementing the coating by cross boundary jump scaling and transition probabilities at the coating surface is developed. Using this formulation, the coating has three distinct impacts on the relaxation rate: an enhancement at small particle sizes, a degradation at intermediate particle sizes, and no effect at large particles sizes. These varied effects are reconciled with the underlying dephasing mechanisms by using the concept of a full dephasing zone to present a physical picture of the dephasing process with and without the coating for all sizes. The enhancement at small particle sizes is studied systemically to demonstrate the existence of an optimal ratio of diffusion coefficients inside/outside the coating to achieve maximal increase in the relaxation rate. Magn Reson Med, 2011.

Simulating the Entropic Collapse of Coarse-Grained Chromosomes

Depletion forces play a role in the compaction and decompaction of chromosomal material in simple cells, but it has remained debatable whether they are sufficient to account for chromosomal collapse. We present coarse-grained molecular dynamics simulations, which reveal that depletion-induced attraction is sufficient to cause the collapse of a flexible chain of large structural monomers immersed in a bath of smaller depletants. These simulations use an explicit coarse-grained computational model that treats both the supercoiled DNA structural monomers and the smaller protein crowding agents as combinatorial, truncated Lennard-Jones spheres. By presenting a simple theoretical model, we quantitatively cast the action of depletants on supercoiled bacterial DNA as an effective solvent quality. The rapid collapse of the simulated flexible chromosome at the predicted volume fraction of depletants is a continuous phase transition. Additional physical effects to such simple chromosome models, such as enthalpic interactions between structural monomers or chain rigidity, are required if the collapse is to be a first-order phase transition.

Memory effects during the unbiased translocation of a polymer through a nanopore.

Through a detailed Langevin dynamics simulation study, the role of memory effects during unbiased translocation is explored. Tests are devised to uncover the presence of memory effects by directly measuring forward/backward-correlated motion as well as the associated change in the dynamics. Conducting these tests at low and high viscosities, a range of behaviours across different time scales is revealed: short-time forward correlations at all viscosities, quasi-static behaviour at low viscosity, and long-time backward correlations at high viscosity. By applying these tests at different portions of the translocation process, these memory effects are also shown to vary as translocation proceeds. Combining this information with standard measurements, a physical picture of unbiased translocation as the diffusion of a local minimum is proposed.

An incremental mean first passage analysis for a quasistatic model of polymer translocation through a nanopore.

For the translocation of a polymer through a nanopore, a quasistatic assumption for the dynamics yields a tractable form for the entropic barrier. Although this is a much simplified model, interesting features such as robust scaling emerge from its application. To explore these details, we present a method of mapping the translocation process as an incremental mean first passage problem. In this approach, the quantity of interest is the average first time t(0) at which the polymer achieves a displacement of Δs in the translocation coordinate s. Constructing scenarios with different initial conditions and boundary conditions, analytic and exact numerical approaches are used to resolve the dynamics of translocation in detail and generate new insight into the nature of the entropic barrier.

Translocation of a Polymer through a Nanopore across a Viscosity Gradient

The translocation of a polymer through a pore in a membrane separating fluids of different viscosities is studied via several computational approaches. Starting with the polymer halfway, we find that as a viscosity difference across the pore is introduced, translocation will predominately occur towards one side of the membrane. These results suggest an intrinsic pumping mechanism for translocation across cell walls which could arise whenever the fluid across the membrane is inhomogeneous. Somewhat surprisingly, the sign of the preferred direction of translocation is found to be strongly dependent on the simulation algorithm: for Langevin dynamics (LD) simulations, a bias towards the low viscosity side is found while for Brownian dynamics (BD), a bias towards the high viscosity is found. Examining the translocation dynamics in detail across a wide range of viscosity gradients and developing a simple force model to estimate the magnitude of the bias, the LD results are demonstrated to be more physically realistic. The LD results are also compared to those generated from a simple, one-dimensional random walk model of translocation to investigate the role of the internal degrees of freedom of the polymer and the entropic barrier. To conclude, the scaling of the results across different polymer lengths demonstrates the saturation of the directional preference with polymer length and the nontrivial location of the maximum in the exponent corresponding to the scaling of the translocation time with polymer length.

Using an incremental mean first passage approach to explore the viscosity dependent dynamics of the unbiased translocation of a polymer through a nanopore

Noting the limitations of the standard characterization of translocation dynamics, an incremental mean first passage process methodology is used to more completely map the unbiased translocation of a polymer through a nanopore. In this approach, the average time t(0) required to reach successively increasing displacements for the first time is recorded - a measure shown to be more commensurate with the mean first passage nature of translocation. Applying this methodology to the results of Langevin dynamics simulations performed in three dimensions across a range of viscosities, a rich set of dynamics spanning regular diffusion at low viscosities to sub-diffusion at higher viscosities is revealed. Further, while the scaling of the net translocation time τ with polymer length N is shown to be viscosity-dependent, common regimes are found across all viscosities: super-diffusive behaviour at short times, an N-independent backbone consistent with τ ∼ N(2.0) at low viscosities and τ ∼ N(2.2) at higher viscosities for intermediate times, and N-dependent deviations from the backbone near the completion of translocation.

Mechanisms of proton spin dephasing in a system of magnetic particles

For protons diffusing among a system of magnetic particles, the process by which initial phase coherence is lost depends substantially on particle size. In this article, evidence for three dephasing mechanisms is presented: an incremental process at small particle sizes (motional averaging regime), a discrete process at intermediate particle sizes (visit limited regime), and a continuous process at large particle sizes (static dephasing regime). While motional averaging regime and static dephasing regime are well known, the distinct dynamics in visit limited regime are often overlooked. Revisiting earlier analytic treatments for the dynamics in this regime, Monte Carlo simulations are performed to extract the details of dephasing and to test the concept of an inner zone of rapid dephasing herein named the full dephasing zone. It is shown that the emergence of a full dephasing zone marks the transition from motional averaging regime to visit limited regime since protons can be fully dephased in a single encounter. Moving from the visit limited regime to the static dephasing regime, a crossover between a purely discrete process and a purely continuous process occurs. Developing a simple model of the dephasing process, the average dephasing time is demonstrated to be relatively constant thus giving insight into the long lasting plateau in the relaxation rate. Magn Reson Med, 2011.