Membrane Remodeling from N-BAR Domain Interactions: Insights from Multi-Scale Simulation

Ayton, Gary S.; Blood, Philip D.; Voth, Gregory A.

doi:10.1529/biophysj.106.101709

Cited by 90 publications

(112 citation statements)

References 42 publications

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“…Such a bilayer possesses local orthotropic symmetry, and its strain energy depends on an additional physical parameter D, referred to as the curvature deviator (40)(41)(42)(43). In addition, similar to the clathrin coat, the BAR coat also stiffens the membrane (44). To incorporate these effects, we prescribe a more generalized bending energy that has a quadratic dependence on D and a corresponding spontaneous curvature D 0 .…”

Section: The Modelmentioning

confidence: 99%

Endocytic proteins drive vesicle growth via instability in high membrane tension environment

Walani

Torres

Agrawal

2015

Proc. Natl. Acad. Sci. U.S.A.

152

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Clathrin-mediated endocytosis (CME) is a key pathway for transporting cargo into cells via membrane vesicles; it plays an integral role in nutrient import, signal transduction, neurotransmission, and cellular entry of pathogens and drug-carrying nanoparticles. Because CME entails substantial local remodeling of the plasma membrane, the presence of membrane tension offers resistance to bending and hence, vesicle formation. Experiments show that in such high-tension conditions, actin dynamics is required to carry out CME successfully. In this study, we build on these pioneering experimental studies to provide fundamental mechanistic insights into the roles of two key endocytic proteins-namely, actin and BAR proteins-in driving vesicle formation in high membrane tension environment. Our study reveals an actin force-induced "snapthrough instability" that triggers a rapid shape transition from a shallow invagination to a highly invaginated tubular structure. We show that the association of BAR proteins stabilizes vesicles and induces a milder instability. In addition, we present a rather counterintuitive role of BAR depolymerization in regulating the shape evolution of vesicles. We show that the dissociation of BAR proteins, supported by actin-BAR synergy, leads to considerable elongation and squeezing of vesicles. Going beyond the membrane geometry, we put forth a stress-based perspective for the onset of vesicle scission and predict the shapes and composition of detached vesicles. We present the snap-through transition and the high in-plane stress as possible explanations for the intriguing direct transformation of broad and shallow invaginations into detached vesicles in BAR mutant yeast cells.clathrin-mediated endocytosis | membrane tension | instability | actin | BAR proteins

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Section: The Modelmentioning

confidence: 99%

Endocytic proteins drive vesicle growth via instability in high membrane tension environment

Walani

Torres

Agrawal

2015

Proc. Natl. Acad. Sci. U.S.A.

152

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“…217 Moreover, Arkhipov et al have recently studied the effectivity with which many N-BAR domains can curve an initially flat bilayer patch 212 using a multiscaling study bridging four scales: from atomistic simulations, over residue-and shape-based coarse-graining up to continuum elasticity.…”

Section: Example Applicationsmentioning

confidence: 99%

Multiscale modeling of emergent materials: biological and soft matter

Murtola

Bunker

Vattulainen

et al. 2009

Phys. Chem. Chem. Phys.

255

234

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On using a too large integration time step in molecular dynamics simulations of coarse-grained molecular models Moritz Winger, Daniel Trzesniak, Riccardo Baron and Wilfred F. In this review, we focus on four current related issues in multiscale modeling of soft and biological matter. First, we discuss how to use structural information from detailed models (or experiments) to construct coarse-grained ones in a hierarchical and systematic way. This is discussed in the context of the so-called Henderson theorem and the inverse Monte Carlo method of Lyubartsev and Laaksonen. In the second part, we take a different look at coarse graining by analyzing conformations of molecules. This is done by the application of self-organizing maps, i.e., a neural network type approach. Such an approach can be used to guide the selection of the relevant degrees of freedom. Then, we discuss technical issues related to the popular dissipative particle dynamics (DPD) method. Importantly, the potentials derived using the inverse Monte Carlo method can be used together with the DPD thermostat. In the final part we focus on solvent-free modeling which offers a different route to coarse graining by integrating out the degrees of freedom associated with solvent.

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“…It is well established that these techniques can provide key insights into the molecular details of bilayers and protein-lipid complexes that are difficult to access by other methods (see for instance refs. 15,16). Most importantly, recent advances in these techniques now allow a detailed characterization of membrane subdomains in much larger spatial and temporal scales (e.g., refs.…”

mentioning

confidence: 99%

Organization, dynamics, and segregation of Ras nanoclusters in membrane domains

Janosi

Hancock

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

160

241

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Recent experiments have shown that membrane-bound Ras proteins form transient, nanoscale signaling platforms that play a crucial role in high-fidelity signal transmission. However, a detailed characterization of these dynamic proteolipid substructures by high-resolution experimental techniques remains elusive. Here we use extensive semiatomic simulations to reveal the molecular basis for the formation and domain-specific distribution of Ras nanoclusters. As model systems, we chose the triply lipidated membrane targeting motif of H-ras (tH) and a large bilayer made up of di16∶0-PC (DPPC), di18∶2-PC (DLiPC), and cholesterol. We found that 4-10 tH molecules assemble into clusters that undergo molecular exchange in the sub-μs to μs time scale, depending on the simulation temperature and hence the stability of lipid domains. Driven by the opposite preference of tH palmitoyls and farnesyl for ordered and disordered membrane domains, clustered tH molecules segregate to the boundary of lipid domains. Additionally, a systematic analysis of depalmitoylated and defarnesylated tH variants allowed us to decipher the role of individual lipid modifications in domain-specific nanocluster localization and thereby explain why homologous Ras isoforms form nonoverlapping nanoclusters. Moreover, the localization of tH nanoclusters at domain boundaries resulted in a significantly lower line tension and increased membrane curvature. Taken together, these results provide a unique mechanistic insight into how protein assembly promoted by lipid-modification modulates bilayer shape to generate functional signaling platforms.lipid bilayer | lipidated Ras proteins | nanoclusters/nanodomains | plasma membrane | molecular dynamics simulation

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Membrane Remodeling from N-BAR Domain Interactions: Insights from Multi-Scale Simulation

Cited by 90 publications

References 42 publications

Endocytic proteins drive vesicle growth via instability in high membrane tension environment

Endocytic proteins drive vesicle growth via instability in high membrane tension environment

Multiscale modeling of emergent materials: biological and soft matter

Organization, dynamics, and segregation of Ras nanoclusters in membrane domains

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