Lipid membrane-mediated attraction between curvature inducing objects (original) (raw)
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LETTERS Aggregation and vesiculation of membrane proteins by curvature-mediated interactions
Membrane remodelling 1-5 plays an important role in cellular tasks such as endocytosis, vesiculation and protein sorting, and in the biogenesis of organelles such as the endoplasmic reticulum or the Golgi apparatus. It is well established that the remodelling process is aided by specialized proteins that can sense 4 as well as create 6 membrane curvature, and trigger tubulation 7-9 when added to synthetic liposomes. Because the energy needed for such largescale changes in membrane geometry significantly exceeds the binding energy between individual proteins and between protein and membrane, cooperative action is essential. It has recently been suggested 10,11 that curvature-mediated attractive interactions could aid cooperation and complement the effects of specific binding events on membrane remodelling. But it is difficult to experimentally isolate curvature-mediated interactions from direct attractions between proteins. Moreover, approximate theories predict repulsion between isotropically curving proteins 12-15 . Here we use coarse-grained membrane simulations to show that curvature-inducing model proteins adsorbed on lipid bilayer membranes can experience attractive interactions that arise purely as a result of membrane curvature. We find that once a minimal local bending is realized, the effect robustly drives protein cluster formation and subsequent transformation into vesicles with radii that correlate with the local curvature imprint. Owing to its universal nature, curvature-mediated attraction can operate even between proteins lacking any specific interactions, such as newly synthesized and still immature membrane proteins in the endoplasmic reticulum.
Three-Body Interactions of Lipid Membrane-Deforming Colloidal Spheres
arXiv (Cornell University), 2023
Many cell functions require a concerted effort from multiple membrane proteins, for example, for signaling, cell division, and endocytosis. One contribution to their successful self-organization stems from the membrane deformations that these proteins induce. While the pairwise interaction potential of two membrane deforming spheres has recently been measured, membrane-deformation induced interactions have been predicted to be non-additive and hence their collective behavior cannot be deduced from this measurement. We here employ a colloidal model system consisting of adhesive spheres and giant unilamellar vesicles to test these predictions by measuring the interaction potential of the simplest case of three membrane-deforming spherical particles. We quantify their interactions and arrangements and for the first time experimentally confirm and quantify the non-additive nature of membrane-deformation induced interactions. We furthermore conclude that there exist two favorable configurations on the membrane: (1) a linear, and (2) a triangular arrangement of the three spheres. Using Monte Carlo simulation we corroborate the experimentally observed energy minima and identify a lowering of the membrane deformation as the cause for the observed configurations. The high symmetry of the preferred arrangements for three particles suggests that arrangements of many membrane-deforming objects might follow simple rules. SIGNIFICANCE Lipid membrane deforming objects, such as proteins, can interact through the membrane curvature they impose. These interactions have been suggested to be non-additive, that is, one cannot extrapolate from the interaction between two objects the interactions between three or more such objects. In addition, the governing equations are so involved that there are only few and contradicting theoretical and numerical predictions. In this manuscript, this interaction is quantified for the first time for three spherically symmetric deformations on spherical membranes through a series of experiments and Monte Carlo simulations. We find two preferred states: a linear arrangement for smaller distances and an equilateral triangle for slightly larger interparticle distances.
Curvature-Driven Migration of Colloids on Tense Lipid Bilayers
Inspired by proteins that generate membrane curvature, sense the underlying membrane geometry, and migrate driven by curvature gradients, we explore the question: Can colloids, adhered to lipid bilayers, also sense and respond to membrane geometry? We report the migration of Janus micro-particles adhered to giant unilamellar vesicles elongated to present spatially varying curvatures. In our experiments, colloids migrate only when the membranes are tense, suggesting that they migrate to minimize membrane area. By determining the energy dissipated along a trajectory, the energy field is inferred to depend on the local deviatoric curvature, like curvature driven capillary migration on interfaces between immiscible fluids. In this latter system, energy gradients are larger, so colloids move deterministically, whereas the paths traced by colloids on vesicles have significant fluctuations. By addressing the role of Brownian motion, we show that the observed migration is analogous to curvature driven capillary migration, with membrane tension playing the role of interfacial tension. Since this motion is mediated by membrane shape, it can be turned on and off by dynamically deforming the vesicle. While particle−particle interactions on lipid membranes have been considered in many contributions, we report here an exciting and previously unexplored modality to actively direct the migration of colloids to desired locations on lipid bilayers.
Mesoscale computational studies of membrane bilayer remodeling by curvature-inducing proteins
Physics Reports
Biological membranes constitute boundaries of cells and cell organelles. These membranes are soft fluid interfaces whose thermodynamic states are dictated by bending moduli, induced curvature fields, and thermal fluctuations. Recently, there has been a flood of experimental evidence highlighting active roles for these structures in many cellular processes ranging from trafficking of cargo to cell motility. It is believed that the local membrane curvature, which is continuously altered due to its interactions with myriad proteins and other macromolecules attached to its surface, holds the key to the emergent functionality in these cellular processes. Mechanisms at the atomic scale are dictated by protein–lipid interaction strength, lipid composition, lipid distribution in the vicinity of the protein, shape and amino acid composition of the protein, and its amino acid contents. The specificity of molecular interactions together with the cooperativity of multiple proteins induce and stabilize complex membrane shapes at the mesoscale. These shapes span a wide spectrum ranging from the spherical plasma membrane to the complex cisternae of the Golgi apparatus. Mapping the relation between the protein-induced deformations at the molecular scale and the resulting mesoscale morphologies is key to bridging cellular experiments across various length scales. In this review, we focus on the theoretical and computational methods used to understand the phenomenology underlying protein-driven membrane remodeling. Interactions at the molecular scale can be computationally probed by all atom and coarse grained molecular dynamics (MD, CGMD), as well as dissipative particle dynamics (DPD) simulations, which we only describe in passing. We choose to focus on several continuum approaches extending the Canham–Helfrich elastic energy model for membranes to include the effect of curvature-inducing proteins and explore the conformational phase space of such systems. In this description, the protein is expressed in the form of a spontaneous curvature field. The approaches include field theoretical methods limited to the small deformation regime, triangulated surfaces and particle-based computational models to investigate the large-deformation regimes observed in the natural state of many biological membranes. Applications of these methods to understand the properties of biological membranes in homogeneous and inhomogeneous environments of proteins, whose underlying curvature fields are either isotropic or anisotropic, are discussed. The diversity in the curvature fields elicits a rich variety of morphological states, including tubes, discs, branched tubes, and caveola. Mapping the thermodynamic stability of these states as a function of tuning parameters such as concentration and strength of curvature induction of the proteins is discussed. The relative stabilities of these self-organized shapes are examined through free-energy calculations. The suite of methods discussed here can be tailored to applications in specific cellular settings such as endocytosis during cargo trafficking and tubulation of filopodial structures in migrating cells, which makes these methods a powerful complement to experimental studies.
Curvature-mediated interactions between membrane proteins
Membrane proteins can deform the lipid bilayer in which they are embedded. If the bilayer is treated as an elastic medium, then these deformations will generate elastic interactions between the proteins. The interaction between a single pair is repulsive. However, for three or more proteins, we show that there are nonpairwise forces whose magnitude is similar to the pairwise forces. When there are five or more proteins, we show that the nonpairwise forces permit the existence of stable protein aggregates, despite their pairwise repulsions.
The Journal of Physical Chemistry Letters, 2014
The mechanism of curvature generation in membranes has been studied for decades due to its important role in many cellular functions. However, it is not clear if, or how, aggregates of lipid-anchored proteins might affect the geometry and elastic property of membranes. As an initial step toward addressing this issue, we performed structural, geometrical, and stress field analyses of coarse-grained molecular dynamics trajectories of a domain-forming bilayer in which an aggregate of lipidated proteins was asymmetrically bound. The results suggest a general mechanism whereby asymmetric incorporation of lipidmodified protein aggregates curve multidomain membranes primarily by expanding the surface area of the monolayer in which the lipid anchor is inserted. SECTION: Biomaterials, Surfactants, and Membranes C ell membranes can adopt different shapes by changing the composition and lateral organization of their constituent lipids and proteins, 1 a phenomenon behind numerous cellular functions including trafficking, motility, and fusion. 2,3 Defective membrane remodeling is implicated in various human diseases, including neuromuscular defects. 4 Many experimental and computational studies have examined membrane remodeling due to changes in lipid acyl chain length and spontaneous curvature, 5−7 shape and hydrophobic length of trans-membrane (TM) proteins, 8,9 and scaffolding or surface area modulation by peripheral proteins. 10,11 Among a variety of computational approaches, coarse-grained molecular dynamics (CGMD) simulations are playing an important role in providing detailed insights into how surface proteins, such as the BAR (Bin− Amphiphysin−Rvs) domain, modulate membrane structure, topology, and elasticity. 12−15 However, few such studies have focused on oligomeric surface proteins. 16 In particular, lack of a suitable molecular system and analysis tools have hampered investigation of curvature generation and/or stabilization by aggregates of lipid-modified proteins, such as nanoclusters of membrane-associated Ras proteins. 17−19 Recently, we described the aggregation of full-length Ras on the surface of a domain-forming lipid bilayer using CGMD. 20 Although the stability and size of the aggregate we obtained was less than ideal due to various factors, such as force field limitations 20,21 and high protein concentration, it can serve as a useful model for probing membrane remolding upon aggregation of lipid-modified proteins on monolayer surfaces. On the technical front, recent work by Ollila et al. 22 and Cui and colleagues 23,24 allow for a detailed characterization of curved membranes through (3D) stress field analysis. Of
Aggregation and vesiculation of membrane proteins by curvature mediated interactions
The Molecular Dynamics simulations were performed at constant temperature and constant pressure using the method described in Ref. (S1) modified to include a dissipative particle dynamics thermostat (DPD) (S2) rather than a Langevin thermostat. The thermostat used a damping parameter of Γ = 1.0 ǫτ /σ 2 , and a cut-off length dcut = 3.0 σ. All simulations were performed at a temperature of kBT = 1.1 ǫ.
Role of particle local curvature in cellular wrapping
2022
Cellular uptake through the lipid membranes plays an important role in adsorbing nutrients and fighting infection and can be used for drug delivery and nanomedicine developments. Endocytosis is one of the known pathways of the cellular uptake which associate with elastic deformation of the membrane wrapping around the foreign particle. The deformability of the membrane itself is strongly regulated by the presence of a cortical cytoskeleton placed underneath the membrane. It has been shown that size, shape, and orientation of the particles influence on their entry into the cell. Here, we study the role of particle local curvature in the cellular uptake by investigating the wrapping of an elastic membrane around a long cylindrical object with an elliptical cross section. The membrane itself is adhered to a substrate mimicking the cytoskeleton. Membrane wrapping proceeds differently whether the initial contact occurs at the particle's highly curved tip (prolate) or along its long side (oblate). We obtain a wrapping phase diagram as a function of the membranecytoskeleton and the membrane-target adhesion energy, which includes three distinct regimes of engulfment(unwrapped, partially wrapped, and fully wrapped), separated by two phase transitions. We also provide analytical expressions for the boundary between the different regimes which confirm that the transitions strongly depend on the orientation and aspect ratio of the particle.