Mechanochemical coupling of lipid organization and protein function through membrane thickness deformations.

Cell membranes are composed of a great variety of protein and lipid species with distinct unperturbed hydrophobic thicknesses. To achieve hydrophobic matching, the lipid bilayer tends to deform around membrane proteins so as to match the protein hydrophobic thickness at bilayer-protein interfaces. Such protein-induced distortions of the lipid bilayer hydrophobic thickness incur a substantial energy cost that depends critically on the bilayer-protein hydrophobic mismatch, while distinct conformational states of membrane proteins often show distinct hydrophobic thicknesses.

Stochastic self-assembly of reaction-diffusion patterns in synaptic membranes.

Synaptic receptor and scaffold molecules self-assemble into membrane protein domains, which play an important role in signal transmission across chemical synapses. Experiment and theory have shown that the formation of receptor-scaffold domains of the characteristic size observed in nerve cells can be understood from the receptor and scaffold reaction and diffusion processes suggested by experiments. We employ here kinetic Monte Carlo (KMC) simulations to explore the self-assembly of synaptic receptor-scaffold domains in a stochastic lattice model of receptor and scaffold reaction-diffusion dynamics.

Regulation of membrane proteins through local heterogeneity in lipid bilayer thickness.

Cell membranes show an intricate organization of lipids and membrane proteins into domains with distinct composition and hydrophobic thickness. Using mechanosensitive ion channels as a model system, we employ the membrane elasticity theory of lipid-protein interactions together with the Landau-Ginzburg theory of lipid domain formation to quantify protein-induced lipid bilayer thickness deformations in lipid bilayers with heterogeneous hydrophobic thickness. We show that protein-induced lipid bilayer thickness deformations yield, without any assumptions about preferential interactions between particular lipid and protein species, organization of lipids and membrane proteins according to their preferred hydrophobic thickness, and couple the conformational states of membrane proteins to the local membrane composition.

Symmetry of membrane protein polyhedra with heterogeneous protein size.

In experiments on membrane protein polyhedral nanoparticles (MPPNs) [Basta et al., Proc. Natl.

Supramolecular organization of membrane proteins with anisotropic hydrophobic thickness.

Experiments have revealed that membrane proteins often self-assemble into locally ordered clusters. Such membrane protein lattices can play key roles in the functional organization of cell membranes. Membrane protein organization can be driven, at least in part, by bilayer-mediated elastic interactions between membrane proteins.

Directed Supramolecular Organization of N-BAR Proteins through Regulation of H0 Membrane Immersion Depth.

Many membrane remodeling events rely on the ability of curvature-generating N-BAR membrane proteins to organize into distinctive supramolecular configurations. Experiments have revealed a conformational switch in N-BAR proteins resulting in vesicular or tubular membrane shapes, with shallow membrane immersion of the H0 amphipathic helices of N-BAR proteins on vesicles but deep H0 immersion on tubes. We develop here a minimal elastic model of the local thinning of the lipid bilayer resulting from H0 immersion.

Do Anti-TNF Agents Increase the Risk of Inflammatory Bowel Disease Evolution in Patients with Ankylosing Spondylitis? Real Life Data.

Objective: The aim of this study was to determine whether there is any association with anti-tumor necrosis factor (TNF) agent administration and development of new-onset inflammatory bowel disease (IBD) in ankylosing spondylitis (AS) patients.

Methods: Records of the patients who met 1984 modified New York criteria for AS between 1998 and 2016 at Rheumatology Department were evaluated retrospectively and data about the patients, IBD properties and medication were obtained.

Results: Among 420 patients, 310 were male, the average age was 42.

Searching for empirical evidence on traffic equilibrium.

Cities around the world are inundated by cars and suffer traffic congestion that results in excess delays, reduced safety and environmental pollution. The interplay between road infrastructure and travel choices defines the level and the spatio-temporal extent of congestion. Given the existing infrastructure, understanding how the route choice decisions are made and how travellers interact with each other is a crucial first step in mitigating traffic congestion.

Distribution of randomly diffusing particles in inhomogeneous media.

Diffusion can be conceptualized, at microscopic scales, as the random hopping of particles between neighboring lattice sites. In the case of diffusion in inhomogeneous media, distinct spatial domains in the system may yield distinct particle hopping rates. Starting from the master equations (MEs) governing diffusion in inhomogeneous media we derive here, for arbitrary spatial dimensions, the deterministic lattice equations (DLEs) specifying the average particle number at each lattice site for randomly diffusing particles in inhomogeneous media.

Stochastic lattice model of synaptic membrane protein domains.

Neurotransmitter receptor molecules, concentrated in synaptic membrane domains along with scaffolds and other kinds of proteins, are crucial for signal transmission across chemical synapses. In common with other membrane protein domains, synaptic domains are characterized by low protein copy numbers and protein crowding, with rapid stochastic turnover of individual molecules. We study here in detail a stochastic lattice model of the receptor-scaffold reaction-diffusion dynamics at synaptic domains that was found previously to capture, at the mean-field level, the self-assembly, stability, and characteristic size of synaptic domains observed in experiments.

Symmetry and Size of Membrane Protein Polyhedral Nanoparticles.

In recent experiments [T. Basta et al., Proc.

Bilayer-thickness-mediated interactions between integral membrane proteins.

Hydrophobic thickness mismatch between integral membrane proteins and the surrounding lipid bilayer can produce lipid bilayer thickness deformations. Experiment and theory have shown that protein-induced lipid bilayer thickness deformations can yield energetically favorable bilayer-mediated interactions between integral membrane proteins, and large-scale organization of integral membrane proteins into protein clusters in cell membranes. Within the continuum elasticity theory of membranes, the energy cost of protein-induced bilayer thickness deformations can be captured by considering compression and expansion of the bilayer hydrophobic core, membrane tension, and bilayer bending, resulting in biharmonic equilibrium equations describing the shape of lipid bilayers for a given set of bilayer-protein boundary conditions.

Architecture and Function of Mechanosensitive Membrane Protein Lattices.

Experiments have revealed that membrane proteins can form two-dimensional clusters with regular translational and orientational protein arrangements, which may allow cells to modulate protein function. However, the physical mechanisms yielding supramolecular organization and collective function of membrane proteins remain largely unknown. Here we show that bilayer-mediated elastic interactions between membrane proteins can yield regular and distinctive lattice architectures of protein clusters, and may provide a link between lattice architecture and lattice function.

Confotronic dynamics of tubular filaments.

Tubular lattices are ubiquitous in nature and technology. Microtubules and nanotubes of all kinds act as important pillars of biological cells and the man-made nano-world. We show that when prestress is introduced in such structures, localized conformational quasiparticles emerge and govern the collective shape dynamics of the lattice.

Dipoles in thin sheets.

A flat elastic sheet may contain pointlike conical singularities that carry a metrical "charge" of Gaussian curvature. Adding such elementary defects to a sheet allows one to make many shapes, in a manner broadly analogous to the familiar multipole construction in electrostatics. However, here the underlying field theory is non-linear, and superposition of intrinsic defects is non-trivial as it must respect the immersion of the resulting surface in three dimensions.