Raft-like lipid mixtures in the highly coarse-grained Cooke membrane model.

Lipid rafts are nanoscopic assemblies of sphingolipids, cholesterol, and specific membrane proteins. They are believed to underlie the experimentally observed lateral heterogeneity of eukaryotic plasma membranes and implicated in many cellular processes, such as signaling and trafficking. Ternary model membranes consisting of saturated lipids, unsaturated lipids, and cholesterol are common proxies because they exhibit phase coexistence between a liquid-ordered (lo) and liquid-disordered (ld) phase and an associated critical point.

Quantifying uncertainty in trans-membrane stresses and moments in simulation.

The lateral stress profile of a lipid bilayer constitutes a valuable link between molecular simulation and mesoscopic elastic theory. Even though it is frequently calculated in simulations, its statistical precision (or that of observables derived from it) is often left unspecified. This omission can be problematic, as uncertainties are prerequisite to assessing statistical significance.

Biomembranes balance many types of leaflet asymmetries.

Many biological membranes host different lipid species in their two leaflets. Since their spontaneous curvatures are typically not the same, this compositional asymmetry generally entails bending torques, which can be counteracted by differential stress-the difference between the two leaflet tensions. This stress, in turn, can affect elastic parameters or phase behavior of the membrane or each individual leaflet, or push easily flippable species, especially cholesterol, from the compressed leaflet into the tense leaflet.

Cell-Surface Binding of DNA Nanostructures for Enhanced Intracellular and Intranuclear Delivery.

DNA nanostructures (DNs) have found increasing use in biosensing, drug delivery, and therapeutics because of their customizable assembly, size and shape control, and facile functionalization. However, their limited cellular uptake and nuclear delivery have hindered their effectiveness in these applications. Here, we demonstrate the potential of applying cell-surface binding as a general strategy to enable rapid enhancement of intracellular and intranuclear delivery of DNs.

Asymmetric membrane "sticky tape" enables simultaneous relaxation of area and curvature in simulation.

Biological lipid membranes are generally asymmetric, not only with respect to the composition of the two membrane leaflets but also with respect to the state of mechanical stress on the two sides. Computer simulations of such asymmetric membranes pose unique challenges with respect to the choice of boundary conditions and ensemble in which such simulations are to be carried out. Here, we demonstrate an alternative to the usual choice of fully periodic boundary conditions: The membrane is only periodic in one direction, with free edges running parallel to the single direction of periodicity.

Elastic and thermodynamic consequences of lipid membrane asymmetry.

Many cellular lipid bilayers consist of leaflets that differ in their lipid composition - a non-equilibrium state actively maintained by cellular sorting processes that counter passive lipid flip-flop. While this lipidomic aspect of membrane asymmetry has been known for half a century, its elastic and thermodynamic ramifications have garnered attention only fairly recently. Notably, the torque arising when lipids of different spontaneous curvature reside in the two leaflets can be counterbalanced by a difference in lateral mechanical stress between them.

Distribution of cholesterol in asymmetric membranes driven by composition and differential stress.

Many lipid membranes of eukaryotic cells are asymmetric, which means the two leaflets differ in at least one physical property, such as lipid composition or lateral stress. Maintaining this asymmetry is helped by the fact that ordinary phospholipids rarely transition between leaflets, but cholesterol is an exception: its flip-flop times are in the microsecond range, so that its distribution between leaflets is determined by a chemical equilibrium. In particular, preferential partitioning can draw cholesterol into a more saturated leaflet, and phospholipid number asymmetry can force it out of a compressed leaflet.

Fluid-gel coexistence in lipid membranes under differential stress.

A widely conserved property of many biological lipid bilayers is their asymmetry. In addition to having distinct compositions on its two sides, a membrane can also exhibit different tensions in its two leaflets, a state known as differential stress. Here, we examine how this stress can influence the phase behavior of the constituent lipid monolayers of a single-component membrane.

Identifying systematic errors in a power spectral analysis of simulated lipid membranes.

The elastic properties of lipid membranes can be measured by monitoring their thermal fluctuations. For instance, comparing the power spectra of membrane shape or lipid director fluctuations with predictions based on suitable continuum theories gives access to bending-, tilt-, and twist-moduli. However, to do so in a computer simulation, we must first define a continuum surface shape and lipid director field from the discrete configurations of lipid molecules in a typically fairly small box.

Stiffening transition in asymmetric lipid bilayers: The role of highly ordered domains and the effect of temperature and size.

Cellular membranes consist of a large variety of lipids and proteins, with a composition that generally differs between the two leaflets of the same bilayer. One consequence of this asymmetry is thought to be the emergence of differential stress, i.e.

Emerging applications at the interface of DNA nanotechnology and cellular membranes: Perspectives from biology, engineering, and physics.

DNA nanotechnology has proven exceptionally apt at probing and manipulating biological environments as it can create nanostructures of almost arbitrary shape that permit countless types of modifications, all while being inherently biocompatible. Emergent areas of particular interest are applications involving cellular membranes, but to fully explore the range of possibilities requires interdisciplinary knowledge of DNA nanotechnology, cell and membrane biology, and biophysics. In this review, we aim for a concise introduction to the intersection of these three fields.

Stabilizing Leaflet Asymmetry under Differential Stress in a Highly Coarse-Grained Lipid Membrane Model.

We present a version of the coarse-grained Cooke lipid model, modified to simulate asymmetric lipid membranes. It is inspired by a method employed by Wang et al. [ 2013, 13, 1093-1106] for artificially penalizing lipid flip-flop but copes more robustly with differential stress, at the cost of one additional bead per lipid and the concomitant increase in computational overhead.

Dynamics of active nematic defects on the surface of a sphere.

A nematic liquid crystal confined to the surface of a sphere exhibits topological defects of total charge +2 due to the topological constraint. In equilibrium, the nematic field forms four +1/2 defects, located at the corners of a regular tetrahedron inscribed within the sphere, since this minimizes the Frank elastic energy. If additionally the individual nematogens exhibit self-driven directional motion, the resulting active system creates large-scale flow that drives it out of equilibrium.

Spontaneous Curvature, Differential Stress, and Bending Modulus of Asymmetric Lipid Membranes.

Lipid bilayers can exhibit asymmetric states, in which the physical characteristics of one leaflet differ from those of the other. This most visibly manifests in a different lipid composition, but it can also involve opposing lateral stresses in each leaflet that combine to an overall vanishing membrane tension. Here, we use theoretical modeling and coarse-grained simulation to explore the interplay between a compositional asymmetry and a nonvanishing differential stress.

Probing Nanoparticle/Membrane Interactions by Combining Amphiphilic Diblock Copolymer Assembly and Plasmonics.

Understanding the interactions between nanoparticles (NPs) and boundaries of cells is crucial both for their toxicity and therapeutic applications. Besides specific receptor-mediated endocytosis of surface-functionalized NPs, passive internalization is prompted by relatively unspecific parameters, such as particle size and charge. Based on theoretical treatments, adhesion to and bending of the cell membrane can induce NP wrapping.

A consistent quadratic curvature-tilt theory for fluid lipid membranes.

The tilt of a lipid molecule describes the deviation of its orientation away from the local normal of its embedding membrane. Tilt is the subleading degree of freedom after a membrane's geometry, and it becomes relevant at scales comparable to lipid bilayer thickness. Building on earlier work by Hamm and Kozlov [Eur.

Mechanical properties of lipid bilayers: a note on the Poisson ratio.

We investigate the Poisson ratio ν of fluid lipid bilayers, i.e., the question how area strains compare to the changes in membrane thickness (or, equivalently, volume) that accompany them.

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 role of scaffold reshaping and disassembly in dynamin driven membrane fission.

The large GTPase dynamin catalyzes membrane fission in eukaryotic cells, but despite three decades of experimental work, competing and partially conflicting models persist regarding some of its most basic actions. Here we investigate the mechanical and functional consequences of dynamin scaffold shape changes and disassembly with the help of a geometrically and elastically realistic simulation model of helical dynamin-membrane complexes. Beyond changes of radius and pitch, we emphasize the crucial role of a third functional motion: an effective rotation of the filament around its longitudinal axis, which reflects alternate tilting of dynamin's PH binding domains and creates a membrane torque.

Optimal Coarse-Grained Site Selection in Elastic Network Models of Biomolecules.

Elastic network models, simple structure-based representations of biomolecules where atoms interact via short-range harmonic potentials, provide great insight into a molecule's internal dynamics and mechanical properties at extremely low computational cost. Their efficiency and effectiveness have made them a pivotal instrument in the computer-aided study of proteins and, since a few years, also of nucleic acids. In general, the coarse-grained sites, i.

Responsive behavior of a branched-chain polymer network: a molecular dynamics study.

Smart polymer hydrogels, which can undergo structural and volume phase transitions in response to external stimuli, have gained much attention for their widespread technological applications. Compared to linear polymers, branched chains offer more extensive opportunities to rationally design functional materials, since they permit more extensive structural tunability-for instance by adjusting the balance between hydrophobic and hydrophilic units, the grafting fraction of backbone monomers, or the side chain length, topology, and solubility. Here we conduct coarse-grained molecular dynamics simulations to assess how well generic physical principles capture this complex interplay of tuning parameters, specifically when building networks from complex branched chains with a hydrophobic backbone.

Dynamin's helical geometry does not destabilize membranes during fission.

It is now widely accepted that dynamin-mediated fission is a fundamentally mechanical process: dynamin undergoes a GTP-dependent conformational change, constricting the neck between two compartments, somehow inducing their fission. However, the exact connection between dynamin's conformational change and the scission of the neck is still unclear. In this paper, we re-evaluate the suggestion that a change in the pitch or radius of dynamin's helical geometry drives the lipid bilayer through a mechanical instability, similar to a well-known phenomenon occurring in soap films.

Novel tilt-curvature coupling in lipid membranes.

On mesoscopic scales, lipid membranes are well described by continuum theories whose main ingredients are the curvature of a membrane's reference surface and the tilt of its lipid constituents. In particular, Hamm and Kozlov [Eur. Phys.

Constriction by Dynamin: Elasticity versus Adhesion.

Any cellular fission process is completed when the neck connecting almost-separate membrane compartments is severed. This crucial step is somehow accomplished by proteins from the dynamin family, which polymerize into helical spirals around such necks. Much research has been devoted to elucidating the specifics of that somehow, but despite no shortage of ideas, the question is not settled.

Effect of intrinsic curvature and edge tension on the stability of binary mixed-membrane three-junctions.

We use a combination of coarse-grained molecular dynamics simulations and theoretical modeling to examine three-junctions in mixed lipid bilayer membranes. These junctions are localized defect lines in which three bilayers merge in such a way that each bilayer shares one monolayer with one of the other two bilayers. The resulting local morphology is non-lamellar, resembling the threefold symmetric defect lines in inverse hexagonal phases, but it regularly occurs during membrane fission and fusion events.