Lateral phase separation of confined membranes

We consider membranes interacting via short, intermediate and long stickers. The effects of the intermediate stickers on the lateral phase separation of the membranes are studied via mean-field approximation. The critical potential depth of the stickers increases in the presence of the intermediate sticker. The lateral phase separation of the membrane thus suppressed by the intermediate stickers. Considering membranes interacting with short and long stickers, the effect of confinement on the phase behavior of the membranes is also investigated analytically

The linear tearing instability in three dimensional, toroidal gyrokinetic simulations

Linear gyro-kinetic simulations of the classical tearing mode in three-dimensional toroidal geometry were performed using the global gyro kinetic turbulence code, GKW . The results were benchmarked against a cylindrical ideal MHD and analytical theory calculations. The stability, growth rate and frequency of the mode were investigated by varying the current profile, collisionality and the pressure gradients. Both collision-less and semi-collisional tearing modes were found with a smooth transition between the two. A residual, finite, rotation frequency of the mode even in the absense of a pressure gradient is observed which is attributed to toroidal finite Larmor-radius effects. When a pressure gradient is present at low collisionality, the mode rotates at the expected electron diamagnetic frequency. However the island rotation reverses direction at high collisionality. The growth rate is found to follow a $\eta^{1/7}$ scaling with collisional resistivity in the semi-collisional regime, closely following the semi-collisional scaling found by Fitzpatrick. The stability of the mode closely follows the stability using resistive MHD theory, however a modification due to toroidal coupling and pressure effects is seen

Adhesion of surfaces via particle adsorption: Exact results for a lattice of fluid columns

We present here exact results for a one-dimensional gas, or fluid, of hard-sphere particles with attractive boundaries. The particles, which can exchange with a bulk reservoir, mediate an interaction between the boundaries. A two-dimensional lattice of such one-dimensional gas `columns' represents a discrete approximation of a three-dimensional gas of particles between two surfaces. The effective particle-mediated interaction potential of the boundaries, or surfaces, is calculated from the grand-canonical partition function of the one-dimensional gas of particles, which is an extension of the well-studied Tonks gas. The effective interaction potential exhibits two minima. The first minimum at boundary contact reflects depletion interactions, while the second minimum at separations close to the particle diameter results from a single adsorbed particle that crosslinks the two boundaries. The second minimum is the global minimum for sufficiently large binding energies of the particles. Interestingly, the effective adhesion energy corresponding to this minimum is maximal at intermediate concentrations of the particles.Comment: to appear in Journal of Statistical Mechanics: Theory and Experimen

Protein-peptide association kinetics beyond the seconds timescale from atomistic simulations

Understanding and control of structures and rates involved in protein-ligand binding are es- sential for drug design. Unfortunately, atomistic molecular dynamics (MD) simulations cannot di- rectly sample the excessively long residence and rearrangement times of tightly binding complexes. Here we exploit the recently developed multi-ensemble Markov model framework to compute full protein-peptide kinetics of the oncoprotein fragment 25−109Mdm2 and the nano-molar inhibitor peptide PMI. Using this system, we report, for the first time, direct estimates of kinetics beyond the seconds timescales using simulations of an all-atom MD model, with high accuracy and pre- cision. These results only require explicit simulations on the sub-milliseconds timescale and are tested against existing mutagenesis data and our own experimental measurements of the dissoci- ation and association rates. The full kinetic model reveals an overall downhill but rugged binding funnel with multiple pathways. The overall strong binding arises from a variety of conformations with different hydrophobic contact surfaces that interconvert on the milliseconds timescale.Funding is acknowledged by European Commission (ERC StG “pcCells” to F.N.), Deutsche Forschungsgemeinschaft (SFB 1114/C3, SFB 740/D7, and TRR 186/A12 to F.N. and SFB 1114/A4 to F.N. and T.W.). J.C. is a Wellcome Trust Senior Research Fellow (WT 095195MA). J.S. is a Marie Sklodowska-Curie Internationally outgoing fellow. M.D.C. is supported by a Biotechnology and Biological Sciences Research Council (BBSRC) studentship

Characterization of a Combined CARS and Interferometric Rayleigh Scattering System

This paper describes the characterization of a combined Coherent anti-Stokes Raman Spectroscopy and Interferometric Rayleigh Scattering (CARS-IRS) system by reporting the accuracy and precision of the measurements of temperature, species mole fraction of N2, O2, and H2, and two-components of velocity. A near-adiabatic H2-air Hencken burner flame was used to provide known properties for measurements made with the system. The measurement system is also demonstrated in a small-scale Mach 1.6 H2-air combustion-heated supersonic jet with a co-flow of H2. The system is found to have a precision that is sufficient to resolve fluctuations of flow properties in the mixing layer of the jet

Curvature-coupling dependence of membrane protein diffusion coefficients

We consider the lateral diffusion of a protein interacting with the curvature of the membrane. The interaction energy is minimized if the particle is at a membrane position with a certain curvature that agrees with the spontaneous curvature of the particle. We employ stochastic simulations that take into account both the thermal fluctuations of the membrane and the diffusive behavior of the particle. In this study we neglect the influence of the particle on the membrane dynamics, thus the membrane dynamics agrees with that of a freely fluctuating membrane. Overall, we find that this curvature-coupling substantially enhances the diffusion coefficient. We compare the ratio of the projected or measured diffusion coefficient and the free intramembrane diffusion coefficient, which is a parameter of the simulations, with analytical results that rely on several approximations. We find that the simulations always lead to a somewhat smaller diffusion coefficient than our analytical approach. A detailed study of the correlations of the forces acting on the particle indicates that the diffusing inclusion tries to follow favorable positions on the membrane, such that forces along the trajectory are on average smaller than they would be for random particle positions.Comment: 16 pages, 8 figure

Impermeability effects in three-dimensional vesicles

We analyse the effects that the impermeability constraint induces on the equilibrium shapes of a three-dimensional vesicle hosting a rigid inclusion. A given alteration of the inclusion and/or vesicle parameters leads to shape modifications of different orders of magnitude, when applied to permeable or impermeable vesicles. Moreover, the enclosed-volume constraint wrecks the uniqueness of stationary equilibrium shapes, and gives rise to pear-shaped or stomatocyte-like vesicles.Comment: 16 pages, 7 figure

The 2018 biomembrane curvature and remodeling roadmap

The importance of curvature as a structural feature of biological membranes has been recognized for many years and has fascinated scientists from a wide range of different backgrounds. On the one hand, changes in membrane morphology are involved in a plethora of phenomena involving the plasma membrane of eukaryotic cells, including endo-and exocytosis, phagocytosis and filopodia formation. On the other hand, a multitude of intracellular processes at the level of organelles rely on generation, modulation, and maintenance of membrane curvature to maintain the organelle shape and functionality. The contribution of biophysicists and biologists is essential for shedding light on the mechanistic understanding and quantification of these processes. Given the vast complexity of phenomena and mechanisms involved in the coupling between membrane shape and function, it is not always clear in what direction to advance to eventually arrive at an exhaustive understanding of this important research area. The 2018 Biomembrane Curvature and Remodeling Roadmap of Journal of Physics D: Applied Physics addresses this need for clarity and is intended to provide guidance both for students who have just entered the field as well as established scientists who would like to improve their orientation within this fascinating area

Membrane-mediated interactions

Interactions mediated by the cell membrane between inclusions, such as membrane proteins or antimicrobial peptides, play important roles in their biological activity. They also constitute a fascinating challenge for physicists, since they test the boundaries of our understanding of self-assembled lipid membranes, which are remarkable examples of two-dimensional complex fluids. Inclusions can couple to various degrees of freedom of the membrane, resulting in different types of interactions. In this chapter, we review the membrane-mediated interactions that arise from direct constraints imposed by inclusions on the shape of the membrane. These effects are generic and do not depend on specific chemical interactions. Hence, they can be studied using coarse-grained soft matter descriptions. We deal with long-range membrane-mediated interactions due to the constraints imposed by inclusions on membrane curvature and on its fluctuations. We also discuss the shorter-range interactions that arise from the constraints on membrane thickness imposed by inclusions presenting a hydrophobic mismatch with the membrane.Comment: 38 pages, 10 figures, pre-submission version. In: Bassereau P., Sens P. (eds) Physics of Biological Membranes. Springer, Cha

Combining Optimal Control Theory and Molecular Dynamics for Protein Folding

A new method to develop low-energy folding routes for proteins is presented. The novel aspect of the proposed approach is the synergistic use of optimal control theory with Molecular Dynamics (MD). In the first step of the method, optimal control theory is employed to compute the force field and the optimal folding trajectory for the atoms of a Coarse-Grained (CG) protein model. The solution of this CG optimization provides an harmonic approximation of the true potential energy surface around the native state. In the next step CG optimization guides the MD simulation by specifying the optimal target positions for the atoms. In turn, MD simulation provides an all-atom conformation whose positions match closely the reference target positions determined by CG optimization. This is accomplished by Targeted Molecular Dynamics (TMD) which uses a bias potential or harmonic restraint in addition to the usual MD potential. Folding is a dynamical process and as such residues make different contacts during the course of folding. Therefore CG optimization has to be reinitialized and repeated over time to accomodate these important changes. At each sampled folding time, the active contacts among the residues are recalculated based on the all-atom conformation obtained from MD. Using the new set of contacts, the CG potential is updated and the CG optimal trajectory for the atoms is recomputed. This is followed by MD. Implementation of this repetitive CG optimization - MD simulation cycle generates the folding trajectory. Simulations on a model protein Villin demonstrate the utility of the method. Since the method is founded on the general tools of optimal control theory and MD without any restrictions, it is widely applicable to other systems. It can be easily implemented with available MD software packages