scholarly journals Curvature-driven feedback on aggregation-diffusion of proteins in lipid bilayers

Soft Matter ◽  
2021 ◽  
Author(s):  
Arijit Mahapatra ◽  
David Saintillan ◽  
Padmini Rangamani
Keyword(s):  
Lipid Bilayers ◽  
Cell Biology ◽  
Membrane Bending ◽  
Curvature Driven

Membrane bending is an extensively studied problem from both modeling and experimental perspectives because of the wide implications of curvature generation in cell biology. Many of the curvature generating aspects...

scholarly journals Curvature-driven feedback on aggregation-diffusion of proteins in lipid bilayers

2021 ◽  
Author(s):  
Arijit Mahapatra ◽  
David Saintillan ◽  
Padmini Rangamani
Keyword(s):  
Lipid Bilayers ◽  
Protein Interactions ◽  
Cell Biology ◽  
Protein Diffusion ◽  
Protein Distribution ◽  
Plane Flow ◽  
Out Of Plane ◽  
Membrane Bending ◽  
Curvature Driven ◽  
And Diffusion

AbstractMembrane bending is an extensively studied problem from both modeling and experimental perspectives because of the wide implications of curvature generation in cell biology. Many of the curvature generating aspects in membranes can be attributed to interactions between proteins and membranes. These interactions include protein diffusion and formation of aggregates due to protein-protein interactions in the plane of the membrane. Recently, we developed a model that couples the in-plane flow of lipids and diffusion of proteins with the out-of-plane bending of the membrane. Building on this work, here, we focus on the role of explicit aggregation of proteins on the surface of the membrane in the presence of membrane bending and diffusion. We develop a comprehensive framework that includes lipid flow, membrane bending energy, the entropy of protein distribution, and an explicit aggregation potential and derive the governing equations. We compare this framework to the Cahn-Hillard formalism to predict the regimes in which the proteins form patterns on the membrane. We demonstrate the utility of this model using numerical simulations to predict how aggregation and diffusion, coupled with curvature generation, can alter the landscape of membrane-protein interactions.

Asymmetry of Structural Characteristics of Lipid Bilayers Induced by Dimethylsulfoxide: An Atomistic Simulation Study

2008 ◽  
Author(s):  
Raghava Alapati ◽  
Dorel Moldovan ◽  
Ram V. Devireddy
Keyword(s):  
Molecular Dynamics ◽  
Lipid Bilayers ◽  
Cell Biology ◽  
Cell Membranes ◽  
Structural Changes ◽  
Cell Damage ◽  
Structural Characteristics ◽  
Cellular Systems ◽  
Freezing Process ◽  
Cryopreservation Protocol

In a typical cryopreservation protocol, the system to be preserved is first equilibrated with chemicals known as cryoprotective agents (CPAs). CPAs have been shown to alleviate cell damage from either the solute effects or the formation of intracellular ice during the subsequent freezing process. Thus, an extensive body of literature reporting the effects of CPAs on cellular systems has been accumulated over the last 50 years; detailing largely experimental interactions between cell systems and chemicals. Recent advances in computational methodology now offer an additional dimension in our ability to understand the molecular interactions between cell membranes, idealized as lipid bilayers and CPAs at atomistic scales. Computer simulations provide unique capabilities for analyzing biomembrane properties from atomistic perspective with a degree of detail that is hard to reach by other techniques. The excellent agreement with the experiment obtained in various molecular dynamics (MD) studies [1] on simple model membranes has raised the confidence in applying the molecular dynamics simulations to even more complex systems. Dimethylsulfoxide (DMSO) is one of the most widely used solvents in cell biology and cryopreservation. During a typical cryopreservation protocol the DMSO composition of aqueous buffers inside and outside of the cell is known to differ considerably. To model and understand the structural changes in cell membranes in such a situation we performed MD simulations of an idealized lipid bilayer membrane which separates two aqueous reservoirs with and without DMSO. Zwitterionic dimyritoylphosphatidylcholine (DMPC) lipid bilayers was chosen as the model membrane.

scholarly journals The Membrane Bending Action of the Syt-1 C2AB Studied on Supported Lipid Bilayers

2015 ◽  
Vol 108 (2) ◽  
pp. 104a ◽  
Author(s):  
Lauren P. MacConnachie ◽  
Neo C. Poyiadji ◽  
Tejeshwar C. Rao ◽  
Arun Anantharam
Keyword(s):  
Lipid Bilayers ◽  
Supported Lipid Bilayers ◽  
Membrane Bending

scholarly journals The conical shape of DIM lipids promotesMycobacterium tuberculosisinfection of macrophages

2019 ◽  
Vol 116 (51) ◽  
pp. 25649-25658 ◽  
Author(s):  
Jacques Augenstreich ◽  
Evert Haanappel ◽  
Guillaume Ferré ◽  
Georges Czaplicki ◽  
Franck Jolibois ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Lipid Bilayers ◽  
Cell Biology ◽  
Biological Response ◽  
Molecular Shape ◽  
General Role ◽  
Ionization Time ◽  
Conical Shape ◽  
Major Virulence Factor ◽  
Molecular Mechanism Of Action

Phthiocerol dimycocerosate (DIM) is a major virulence factor of the pathogenMycobacterium tuberculosis(Mtb). While this lipid promotes the entry ofMtbinto macrophages, which occurs via phagocytosis, its molecular mechanism of action is unknown. Here, we combined biophysical, cell biology, and modeling approaches to reveal the molecular mechanism of DIM action on macrophage membranes leading to the first step ofMtbinfection. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry showed that DIM molecules are transferred from theMtbenvelope to macrophage membranes during infection. Multiscale molecular modeling and31P-NMR experiments revealed that DIM adopts a conical shape in membranes and aggregates in the stalks formed between 2 opposing lipid bilayers. Infection of macrophages pretreated with lipids of various shapes uncovered a general role for conical lipids in promoting phagocytosis. Taken together, these results reveal how the molecular shape of a mycobacterial lipid can modulate the biological response of macrophages.

scholarly journals Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Madhurima Dhara ◽  
Maria Mantero Martinez ◽  
Mazen Makke ◽  
Yvonne Schwarz ◽  
Ralf Mohrmann ◽  
...  
Keyword(s):  
Active Role ◽  
Underlying Mechanism ◽  
Membrane Curvature ◽  
Transmembrane Domains ◽  
Snare Complex ◽  
Fusion Pore ◽  
Pore Evolution ◽  
Tightly Coupled ◽  
Membrane Bending ◽  
Curvature Driven

Vesicle fusion is mediated by assembly of SNARE proteins between opposing membranes. While previous work suggested an active role of SNARE transmembrane domains (TMDs) in promoting membrane merger (Dhara et al., 2016), the underlying mechanism remained elusive. Here, we show that naturally-occurring v-SNARE TMD variants differentially regulate fusion pore dynamics in mouse chromaffin cells, indicating TMD flexibility as a mechanistic determinant that facilitates transmitter release from differentially-sized vesicles. Membrane curvature-promoting phospholipids like lysophosphatidylcholine or oleic acid profoundly alter pore expansion and fully rescue the decelerated fusion kinetics of TMD-rigidifying VAMP2 mutants. Thus, v-SNARE TMDs and phospholipids cooperate in supporting membrane curvature at the fusion pore neck. Oppositely, slowing of pore kinetics by the SNARE-regulator complexin-2 withstands the curvature-driven speeding of fusion, indicating that pore evolution is tightly coupled to progressive SNARE complex formation. Collectively, TMD-mediated support of membrane curvature and SNARE force-generated membrane bending promote fusion pore formation and expansion.

scholarly journals Beyond Langmuir: surface-bound macromolecule condensates

2020 ◽  
Vol 31 (23) ◽  
pp. 2502-2508
Author(s):  
T. J. Mitchison
Keyword(s):  
Phase Separation ◽  
Lipid Bilayers ◽  
Cell Biology ◽  
Test Case ◽  
Surface Binding ◽  
Multilayer Adsorption ◽  
Low Concentrations ◽  
Binding Surface ◽  
Bet Theory ◽  
Physical Biochemistry

Macromolecule condensates, phase separation, and membraneless compartments have become an important area of cell biology research where new biophysical concepts are emerging. This article discusses the possibility that condensates assemble on multivalent surfaces such as DNA, microtubules, or lipid bilayers by multilayer adsorption. Langmuir isotherm theory conceptualized saturable surface binding and deeply influenced physical biochemistry. Brunauer-Emmett-Teller (BET) theory extended Langmuir’s ideas to multilayer adsorption. A BET-inspired biochemical model predicts that surface-binding proteins with a tendency to self-associate will form multilayered condensates on binding surfaces. These “bound condensates” are expected to assemble well below the saturation concentration for liquid–liquid phase separation, so they can compete subunits away from phase-separated droplets and are thermodynamically pinned to the binding surface. Tau binding to microtubules is an interesting test case. The nonsaturable binding isotherm is reminiscent of BET predictions, but assembly of Tau-rich domains at low concentrations requires a different model. Surface-bound condensates may find multiple biological uses, particularly in situations where it is important that condensate assembly is spatially constrained, such as gene regulation.

scholarly journals Transport Phenomena in Fluid Films with Curvature Elasticity

2020 ◽  
Author(s):  
Arijit Mahapatra ◽  
David Saintillan ◽  
Padmini Rangamani
Keyword(s):  
Lipid Bilayers ◽  
Chemical Potential ◽  
Equations Of Motion ◽  
Transport Processes ◽  
Spontaneous Curvature ◽  
Protein Diffusion ◽  
Coupled Transport ◽  
Fluid Films ◽  
Elastic Energy Density ◽  
Membrane Bending

AbstractCellular membranes are elastic lipid bilayers that contain a variety of proteins, including ion channels, receptors, and scaffolding proteins. These proteins are known to diffuse in the plane of the membrane and to influence the bending of the membrane. Experiments have shown that lipid flow in the plane of the membrane is closely coupled with the diffusion of proteins. Thus there is a need for a comprehensive framework that accounts for the interplay between these processes. Here, we present a theory for the coupled in-plane viscous flow of lipids, diffusion of transmembrane proteins, and curvature elastic deformation of lipid bilayers. The proteins in the membrane are modeled such that they influence membrane bending by inducing a spontaneous curvature. We formulate the free energy of the membrane with a Helfrich-like curvature elastic energy density function modified to account for the chemical potential energy of proteins. We derive the conservation laws and equations of motion for this system. Finally, we present results from dimensional analysis and numerical simulations and demonstrate the effect of coupled transport processes in governing the dynamics of membrane bending and protein diffusion.

scholarly journals The influence of phosphatidylserine localisation and lipid phase on membrane remodelling by the ESCRT-II/ESCRT-III complex

2020 ◽  
Author(s):  
Andrew Booth ◽  
Christopher J. Marklew ◽  
Barbara Ciani ◽  
Paul A. Beales
Keyword(s):  
Lipid Bilayers ◽  
Electrostatic Interactions ◽  
Annexin V ◽  
Membrane Curvature ◽  
Lipid Phase ◽  
Membrane Mechanics ◽  
Anionic Phospholipids ◽  
Escrt Complex ◽  
Phospholipid Distribution ◽  
Curvature Driven

AbstractThe endosomal sorting complex required for transport (ESCRT) organises in supramolecular structures on the surface of lipid bilayers to drive membrane invagination and scission of intraluminal vesicles (ILVs), a process also controlled by membrane mechanics. However, ESCRT association with the membrane is also mediated by electrostatic interactions with anionic phospholipids. Phospholipid distribution within natural biomembranes is inhomogeneous due to, for example, the formation of lipid rafts and curvature-driven lipid sorting. Here, we have used phase-separated giant unilamellar vesicles (GUVs) to investigate the link between phosphatidylserine (PS)-rich lipid domains and ESCRT activity. We employ GUVs composed of phase separating lipid mixtures, where unsaturated DOPS and saturated DPPS lipids are incorporated individually or simultaneously to enhance PS localisation in liquid disordered (Ld) and/or liquid ordered (Lo) domains, respectively. PS partitioning between the coexisting phases is confirmed by a fluorescent Annexin V probe. Ultimately, we find that ILV generation promoted by ESCRTs is significantly enhanced when PS lipids localise within Ld domains. However, the ILVs that form are rich in Lo lipids. We interpret this surprising observation as preferential recruitment of the Lo phase beneath the ESCRT complex due to its increased rigidity, where the Ld phase is favoured in the neck of the resultant buds to facilitate the high membrane curvature in these regions of the membrane during the ILV formation process. Ld domains offer lower resistance to membrane bending, demonstrating a mechanism by which the composition and mechanics of membranes can be coupled to regulate the location and efficiency of ESCRT activity.

Curvature-driven adsorption of cationic nanoparticles to phase boundaries in multicomponent lipid bilayers

Nanoscale ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 2767-2778 ◽  
Author(s):  
Jonathan K. Sheavly ◽  
Joel A. Pedersen ◽  
Reid C. Van Lehn
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Lipid Bilayers ◽  
Negative Curvature ◽  
Free Energy Calculations ◽  
Coarse Grained ◽  
Phase Boundaries ◽  
Cationic Nanoparticles ◽  
Dynamics Simulations ◽  
Curvature Driven

Coarse-grained molecular dynamics simulations and free energy calculations reveal that cationic nanoparticles preferentially adsorb to regions of intrinsic negative curvature at phase boundaries in multicomponent lipid bilayers.

scholarly journals Physical basis of some membrane shaping mechanisms

2016 ◽  
Vol 374 (2072) ◽  
pp. 20160034 ◽  
Author(s):  
Mijo Simunovic ◽  
Coline Prévost ◽  
Andrew Callan-Jones ◽  
Patricia Bassereau
Keyword(s):  
Optical Tweezers ◽  
Cell Biology ◽  
Soft Matter ◽  
Bulk Diffusion ◽  
Theoretical Models ◽  
Membrane Curvature ◽  
Transport Pathways ◽  
Bar Domain ◽  
Membrane Bending ◽  
Or Gene

In vesicular transport pathways, membrane proteins and lipids are internalized, externalized or transported within cells, not by bulk diffusion of single molecules, but embedded in the membrane of small vesicles or thin tubules. The formation of these ‘transport carriers’ follows sequential events: membrane bending, fission from the donor compartment, transport and eventually fusion with the acceptor membrane. A similar sequence is involved during the internalization of drug or gene carriers inside cells. These membrane-shaping events are generally mediated by proteins binding to membranes. The mechanisms behind these biological processes are actively studied both in the context of cell biology and biophysics. Bin/amphiphysin/Rvs (BAR) domain proteins are ideally suited for illustrating how simple soft matter principles can account for membrane deformation by proteins. We review here some experimental methods and corresponding theoretical models to measure how these proteins affect the mechanics and the shape of membranes. In more detail, we show how an experimental method employing optical tweezers to pull a tube from a giant vesicle may give important quantitative insights into the mechanism by which proteins sense and generate membrane curvature and the mechanism of membrane scission. This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.

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