laboratoire de physique statistique
 
 
laboratoire de physique statistique

Publications

Rechercher
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 


35
P U B L I C A T I O N S



 
2016
Fluctuating fitness shapes the clone-size distribution of immune repertoires - Desponds, Jonathan and Mora, Thierry and Walczak, Aleksandra M.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113274-279 (2016)

Abstract : The adaptive immune system relies on the diversity of receptors expressed on the surface of B-and T cells to protect the organism from a vast amount of pathogenic threats. The proliferation and degradation dynamics of different cell types (B cells, T cells, naive, memory) is governed by a variety of antigenic and environmental signals, yet the observed clone sizes follow a universal power-law distribution. Guided by this reproducibility we propose effective models of somatic evolution where cell fate depends on an effective fitness. This fitness is determined by growth factors acting either on clones of cells with the same receptor responding to specific antigens, or directly on single cells with no regard for clones. We identify fluctuations in the fitness acting specifically on clones as the essential ingredient leading to the observed distributions. Combining our models with experiments, we characterize the scale of fluctuations in antigenic environments and we provide tools to identify the relevant growth signals in different tissues and organisms. Our results generalize to any evolving population in a fluctuating environment.
Snapshot of sequential SNARE assembling states between membranes shows that N-terminal transient assembly initializes fusion - Wang, Yong Jian and Li, Feng and Rodriguez, Nicolas and Lafosse, Xavier and Gourier, Christine and Perez, Eric and Pincet, Frederic
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1133533-3538 (2016)

Abstract : Many prominent biological processes are driven by protein assembling between membranes. Understanding the mechanisms then entails determining the assembling pathway of the involved proteins. Because the intermediates are by nature transient and located in the intermembrane space, this determination is generally a very difficult, not to say intractable, problem. Here, by designing a setup with sphere/plane geometry, we have been able to freeze one transient state in which the N-terminal domains of SNARE proteins are assembled. A single camera frame is sufficient to obtain the complete probability of this state with the transmembrane distance. We show that it forms when membranes are 20 nm apart and stabilizes by further assembling of the SNAREs at 8 nm. This setup that fixes the intermembrane distance, and thereby the transient states, while optically probing the level of molecular assembly by Forster resonance energy transfer (FRET) can be used to characterize any other transient transmembrane complexes.
Diversity of immune strategies explained by adaptation to pathogen statistics - Mayer, Andreas and Mora, Thierry and Rivoire, Olivier and Walczak, Aleksandra M.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1138630-8635 (2016)

Abstract : Biological organisms have evolved a wide range of immune mechanisms to defend themselves against pathogens. Beyond molecular details, these mechanisms differ in how protection is acquired, processed, and passed on to subsequent generations-differences that may be essential to long-term survival. Here, we introduce a mathematical framework to compare the long-term adaptation of populations as a function of the pathogen dynamics that they experience and of the immune strategy that they adopt. We find that the two key determinants of an optimal immune strategy are the frequency and the characteristic timescale of the pathogens. Depending on these two parameters, our framework identifies distinct modes of immunity, including adaptive, innate, bet-hedging, and CRISPR-like immunities, which recapitulate the diversity of natural immune systems.
Kinetic barriers to SNAREpin assembly in the regulation of membrane docking/priming and fusion - Li, Feng and Tiwari, Neeraj and Rothman, James E. and Pincet, Frederic
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 11310536-10541 (2016)

Abstract : Neurotransmission is achieved by soluble NSF attachment protein receptor (SNARE)-driven fusion of readily releasable vesicles that are docked and primed at the presynaptic plasma membrane. After neurotransmission, the readily releasable pool of vesicles must be refilled in less than 100 ms for subsequent release. Here we show that the initial association of SNARE complexes, SNAREpins, is far too slow to support this rapid refilling owing to an inherently high activation energy barrier. Our data suggest that acceleration of this process, i.e., lowering of the barrier, is physiologically necessary and can be achieved by molecular factors. Furthermore, under zero force, a low second energy barrier transiently traps SNAREpins in a half-zippered state similar to the partial assembly that engages calcium-sensitive regulatory machinery. This result suggests that the barrier must be actively raised in vivo to generate a sufficient pause in the zippering process for the regulators to set in place. We show that the heights of the activation energy barriers can be selectively changed by molecular factors. Thus, it is possible to modify, both in vitro and in vivo, the lifespan of each metastable state. This controllability provides a simple model in which vesicle docking/priming, an intrinsically slow process, can be substantially accelerated. It also explains how the machinery that regulates vesicle fusion can be set in place while SNAREpins are trapped in a half-zippered state.
Surfactant adsorption kinetics in microfluidics - Riechers, Birte and Maes, Florine and Akoury, Elias and Semin, Benoit and Gruner, Philipp and Baret, Jean-Christophe
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 11311465-11470 (2016)

Abstract : Emulsions are metastable dispersions. Their lifetimes are directly related to the dynamics of surfactants. We design a microfluidic method to measure the kinetics of adsorption of surfactants to the droplet interface, a key process involved in foaming, emulsification, and droplet coarsening. The method is based on the pH decay in the droplet as a direct measurement of the adsorption of a carboxylic acid surfactant to the interface. From the kinetic measurement of the bulk equilibration of the pH, we fully determine the adsorption process of the surfactant. The small droplet size and the convection during the droplet flow ensure that the transport of surfactant through the bulk is not limiting the kinetics of adsorption. To validate our measurements, we show that the adsorption process determines the timescale required to stabilize droplets against coalescence, and we show that the interface should be covered at more than 90\% to prevent coalescence. We therefore quantitatively link the process of adsorption/desorption, the stabilization of emulsions, and the kinetics of solute partitioning-here through ion exchange-unraveling the timescales governing these processes. Our method can be further generalized to other surfactants, including nonionic surfactants, by making use of fluorophore-surfactant interactions.
Stability, folding dynamics, and long-range conformational transition of the synaptic t-SNARE complex - Zhang, Xinming and Rebane, Aleksander A. and Ma, Lu and Li, Feng and Jiao, Junyi and Qu, Hong and Pincet, Frederic and Rothman, James E. and Zhang, Yongli
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113E8031-E8040 (2016)

Abstract : Synaptic soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) couple their stepwise folding to fusion of synaptic vesicles with plasma membranes. In this process, three SNAREs assemble into a stable four-helix bundle. Arguably, the first and rate-limiting step of SNARE assembly is the formation of an activated binary target (t)-SNARE complex on the target plasma membrane, which then zippers with the vesicle (v)-SNARE on the vesicle to drive membrane fusion. However, the t-SNARE complex readily misfolds, and its structure, stability, and dynamics are elusive. Using single-molecule force spectroscopy, we modeled the synaptic t-SNARE complex as a parallel three-helix bundle with a small frayed C terminus. The helical bundle sequentially folded in an N-terminal domain (NTD) and a C-terminal domain (CTD) separated by a central ionic layer, with total unfolding energy of similar to 17 k(B)T, where kB is the Boltzmann constant and T is 300 K. Peptide binding to the CTD activated the t-SNARE complex to initiate NTD zippering with the v-SNARE, a mechanism likely shared by the mammalian uncoordinated-18-1 protein (Munc18-1). The NTD zippering then dramatically stabilized the CTD, facilitating further SNARE zippering. The subtle bidirectional t-SNARE conformational switch was mediated by the ionic layer. Thus, the t-SNARE complex acted as a switch to enable fast and controlled SNARE zippering required for synaptic vesicle fusion and neurotransmission.
 
2015
Inferring epigenetic dynamics from kin correlations - Hormoz, Sahand and Desprat, Nicolas and Shraiman, Boris I.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 112E2281-E2289 (2015)

Abstract : Populations of isogenic embryonic stem cells or clonal bacteria often exhibit extensive phenotypic heterogeneity that arises from intrinsic stochastic dynamics of cells. The phenotypic state of a cell can be transmitted epigenetically in cell division, leading to correlations in the states of cells related by descent. The extent of these correlations is determined by the rates of transitions between the phenotypic states. Therefore, a snapshot of the phenotypes of a collection of cells with known genealogical structure contains information on phenotypic dynamics. Here, we use a model of phenotypic dynamics on a genealogical tree to define an inference method that allows extraction of an approximate probabilistic description of the dynamics from observed phenotype correlations as a function of the degree of kinship. The approach is tested and validated on the example of Pyoverdine dynamics in Pseudomonas aeruginosa colonies. Interestingly, we find that correlations among pairs and triples of distant relatives have a simple but nontrivial structure indicating that observed phenotypic dynamics on the genealogical tree is approximately conformal-a symmetry characteristic of critical behavior in physical systems. The proposed inference method is sufficiently general to be applied in any system where lineage information is available.
How a well-adapted immune system is organized - Mayer, Andreas and Balasubramanian, Vijay and Mora, Thierry and Walczak, Aleksandra M.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1125950-5955 (2015)

Abstract : The repertoire of lymphocyte receptors in the adaptive immune system protects organisms from diverse pathogens. A well-adapted repertoire should be tuned to the pathogenic environment to reduce the cost of infections. We develop a general framework for predicting the optimal repertoire that minimizes the cost of infections contracted from a given distribution of pathogens. The theory predicts that the immune system will have more receptors for rare antigens than expected from the frequency of encounters; individuals exposed to the same infections will have sparse repertoires that are largely different, but nevertheless exploit cross-reactivity to provide the same coverage of antigens; and the optimal repertoires can be reached via the dynamics of competitive binding of antigens by receptors and selective amplification of stimulated receptors. Our results follow from a tension between the statistics of pathogen detection, which favor a broader receptor distribution, and the effects of cross-reactivity, which tend to concentrate the optimal repertoire onto a few highly abundant clones. Our predictions can be tested in high-throughput surveys of receptor and pathogen diversity.
Thermodynamics and signatures of criticality in a network of neurons - Tkacik, Gasper and Mora, Thierry and Marre, Olivier and Amodei, Dario and Palmer, Stephanie E. and Berry, II, Michael J. and Bialek, William
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 11211508-11513 (2015)

Abstract : The activity of a neural network is defined by patterns of spiking and silence from the individual neurons. Because spikes are (relatively) sparse, patterns of activity with increasing numbers of spikes are less probable, but, with more spikes, the number of possible patterns increases. This tradeoff between probability and numerosity is mathematically equivalent to the relationship between entropy and energy in statistical physics. We construct this relationship for populations of up to N = 160 neurons in a small patch of the vertebrate retina, using a combination of direct and model-based analyses of experiments on the response of this network to naturalistic movies. We see signs of a thermodynamic limit, where the entropy per neuron approaches a smooth function of the energy per neuron as N increases. The form of this function corresponds to the distribution of activity being poised near an unusual kind of critical point. We suggest further tests of criticality, and give a brief discussion of its functional significance.
DOI
10
Distinguishing the immunostimulatory properties of noncoding RNAs expressed in cancer cells - Tanne, Antoine and Muniz, Luciana R. and Puzio-Kuter, Anna and Leonova, Katerina I. and Gudkov, Andrei V. and Ting, David T. and Monasson, Remi and Cocco, Simona and Levine, Arnold J. and Bhardwaj, Nina and Greenbaum, Benjamin D.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 11215154-15159 (2015)

Abstract : Recent studies have demonstrated abundant transcription of a set of noncoding RNAs (ncRNAs) preferentially within tumors as opposed to normal tissue. Using an approach from statistical physics, we quantify global transcriptome-wide motif use for the first time, to our knowledge, in human and murine ncRNAs, determining that most have motif use consistent with the coding genome. However, an outlier subset of tumor-associated ncRNAs, typically of recent evolutionary origin, has motif use that is often indicative of pathogen-associated RNA. For instance, we show that the tumor-associated human repeat human satellite repeat II (HSATII) is enriched in motifs containing CpG dinucleotides in AU-rich contexts that most of the human genome and human adapted viruses have evolved to avoid. We demonstrate that a key subset of these ncRNAs functions as immunostimulatory ``self-agonists'' and directly activates cells of the mononuclear phagocytic system to produce proinflammatory cytokines. These ncRNAs arise from endogenous repetitive elements that are normally silenced, yet are often very highly expressed in cancers. We propose that the innate response in tumors may partially originate from direct interaction of immunogenic ncRNAs expressed in cancer cells with innate pattern recognition receptors, and thereby assign a previously unidentified danger-associated function to a set of dark matter repetitive elements. These findings potentially reconcile several observations concerning the role of ncRNA expression in cancers and their relationship to the tumor microenvironment.
 
2014
DOI
11
Modeling quantum fluid dynamics at nonzero temperatures - Berloff, Natalia G. and Brachet, Marc and Proukakis, Nick P.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1114675-4682 (2014)

Abstract : The detailed understanding of the intricate dynamics of quantum fluids, in particular in the rapidly growing subfield of quantum turbulence which elucidates the evolution of a vortex tangle in a superfluid, requires an in-depth understanding of the role of finite temperature in such systems. The Landau two-fluidmodel is the most successful hydrodynamical theory of superfluid helium, but by the nature of the scale separations it cannot give an adequate description of the processes involving vortex dynamics and interactions. In our contribution we introduce a framework based on a nonlinear classical-field equation that is mathematically identical to the Landau model and provides a mechanism for severing and coalescence of vortex lines, so that the questions related to the behavior of quantized vortices can be addressed self-consistently. The correct equation of state as well as nonlocality of interactions that leads to the existence of the roton minimum can also be introduced in such description. We review and apply the ideas developed for finite-temperature description of weakly interacting Bose gases as possible extensions and numerical refinements of the proposed method. We apply this method to elucidate the behavior of the vortices during expansion and contraction following the change in applied pressure. We show that at low temperatures, during the contraction of the vortex core as the negative pressure grows back to positive values, the vortex line density grows through a mechanism of vortex multiplication. This mechanism is suppressed at high temperatures.
DOI
12
Quantitative theory of entropic forces acting on constrained nucleotide sequences applied to viruses - Greenbaum, Benjamin D. and Cocco, Simona and Levine, Arnold J. and Monasson, Remi
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1115054-5059 (2014)

Abstract : We outline a theory to quantify the interplay of entropic and selective forces on nucleotide organization and apply it to the genomes of single-stranded RNA viruses. We quantify these forces as intensive variables that can easily be compared between sequences, outline a computationally efficient transfer-matrix method for their calculation, and apply this method to influenza and HIV viruses. We find viruses altering their dinucleotide motif use under selective forces, with these forces on CpG dinucleotides growing stronger in influenza the longer it replicates in humans. For a subset of genes in the human genome, many involved in antiviral innate immunity, the forces acting on CpG dinucleotides are even greater than the forces observed in viruses, suggesting that both effects are in response to similar selective forces involving the innate immune system. We further find that the dynamics of entropic forces balancing selective forces can be used to predict how long it will take a virus to adapt to a new host, and that it would take H1N1 several centuries to adapt to humans from birds, typically contributing many of its synonymous substitutions to the forcible removal of CpG dinucleotides. By examining the probability landscape of dinucleotide motifs, we predict where motifs are likely to appear using only a single-force parameter and uncover the localization of UpU motifs in HIV. Essentially, we extend the natural language and concepts of statistical physics, such as entropy and conjugated forces, to understanding viral sequences and, more generally, constrained genome evolution.
DOI
13
Social interactions dominate speed control in poising natural flocks near criticality - Bialek, William and Cavagna, Andrea and Giardina, Irene and Mora, Thierry and Pohl, Oliver and Silvestri, Edmondo and Viale, Massimiliano and Walczak, Aleksandra M.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1117212-7217 (2014)

Abstract : Flocks of birds exhibit a remarkable degree of coordination and collective response. It is not just that thousands of individuals fly, on average, in the same direction and at the same speed, but that even the fluctuations around the mean velocity are correlated over long distances. Quantitative measurements on flocks of starlings, in particular, show that these fluctuations are scale-free, with effective correlation lengths proportional to the linear size of the flock. Here we construct models for the joint distribution of velocities in the flock that reproduce the observed local correlations between individuals and their neighbors, as well as the variance of flight speeds across individuals, but otherwise have as little structure as possible. These minimally structured or maximum entropy models provide quantitative, parameter-free predictions for the spread of correlations throughout the flock, and these are in excellent agreement with the data. These models are mathematically equivalent to statistical physics models for ordering in magnets, and the correct prediction of scale-free correlations arises because the parameters-completely determined by the data-are in the critical regime. In biological terms, criticality allows the flock to achieve maximal correlation across long distances with limited speed fluctuations.
DOI
14
Quantifying selection in immune receptor repertoires - Elhanati, Yuval and Murugan, Anand and Callan, Jr., Curtis G. and Mora, Thierry and Walczak, Aleksandra M.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1119875-9880 (2014)

Abstract : The efficient recognition of pathogens by the adaptive immune system relies on the diversity of receptors displayed at the surface of immune cells. T-cell receptor diversity results from an initial random DNA editing process, called VDJ recombination, followed by functional selection of cells according to the interaction of their surface receptors with self and foreign antigenic peptides. Using high-throughput sequence data from the beta-chain of human T-cell receptors, we infer factors that quantify the overall effect of selection on the elements of receptor sequence composition: the V and J gene choice and the length and amino acid composition of the variable region. We find a significant correlation between biases induced by VDJ recombination and our inferred selection factors together with a reduction of diversity during selection. Both effects suggest that natural selection acting on the recombination process has anticipated the selection pressures experienced during somatic evolution. The inferred selection factors differ little between donors or between naive and memory repertoires. The number of sequences shared between donors is well-predicted by our model, indicating a stochastic origin of such public sequences. Our approach is based on a probabilistic maximum likelihood method, which is necessary to disentangle the effects of selection from biases inherent in the recombination process.
DOI
15
Calcium sensitive ring-like oligomers formed by synaptotagmin - Wang, Jing and Bello, Oscar and Auclair, Sarah M. and Wang, Jing and Coleman, Jeff and Pincet, Frederic and Krishnakumar, Shyam S. and Sindelar, Charles V. and Rothman, James E.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 11113966-13971 (2014)

Abstract : The synaptic vesicle protein synaptotagmin-1 (SYT) is required to couple calcium influx to the membrane fusion machinery. However, the structural mechanism underlying this process is unclear. Here we report an unexpected circular arrangement (ring) of SYT's cytosolic domain (C2AB) formed on lipid monolayers in the absence of free calcium ions as revealed by electron microscopy. Rings vary in diameter from 18-43 nm, corresponding to 11-26 molecules of SYT. Continuous stacking of the SYT rings occasionally converts both lipid monolayers and bilayers into protein-coated tubes. Helical reconstruction of the SYT tubes shows that one of the C2 domains (most likely C2B, based on its biochemical properties) interacts with the membrane and is involved in ring formation, and the other C2 domain points radially outward. SYT rings are disrupted rapidly by physiological concentrations of free calcium but not by magnesium. Assuming that calcium-free SYT rings are physiologically relevant, these results suggest a simple and novel mechanism by which SYT regulates neurotransmitter release: The ring acts as a spacer to prevent the completion of the soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) complex assembly, thereby clamping fusion in the absence of calcium. When the ring disassembles in the presence of calcium, fusion proceeds unimpeded.
 
2013
DOI
16
Anisotropic growth shapes intestinal tissues during embryogenesis - Ben Amar, Martine and Jia, Fei
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 11010525-10530 (2013)

Abstract : Embryogenesis offers a real laboratory for pattern formation, buckling, and postbuckling induced by growth of soft tissues. Each part of our body is structured in multiple adjacent layers: the skin, the brain, and the interior of organs. Each layer has a complex biological composition presenting different elasticity. Generated during fetal life, these layers will experience growth and remodeling in the early postfertilization stages. Here, we focus on a herringbone pattern occurring in fetal intestinal tissues. Common to many mammalians, this instability is a precursor of the villi, finger-like projections into the lumen. For avians (chicks' and turkeys' embryos), it has been shown that, a few days after fertilization, the mucosal epithelium of the duodenum is smooth, and then folds emerge, which present 2 d later a pronounced zigzag instability. Many debates and biological studies are devoted to this specific morphology, which regulates the cell renewal in the intestine. After reviewing experimental results about duodenum morphogenesis, we show that a model based on simplified hypothesis for the growth of the mesenchyme can explain buckling and postbuckling instabilities. Being completely analytical, it is based on biaxial compressive stresses due to differential growth between layers and it predicts quantitatively the morphological changes. The growth anisotropy increasing with time, the competition between folds and zigzags, is proved to occur as a secondary instability. The model is compared with available experimental data on chick's duodenum and can be applied to other intestinal tissues, the zigzag being a common and spectacular microstructural pattern of intestine embryogenesis.
DOI
17
Cell-cell contacts confine public goods diffusion inside Pseudomonas aeruginosa clonal microcolonies - Julou, Thomas and Mora, Thierry and Guillon, Laurent and Croquette, Vincent and Schalk, Isabelle J. and Bensimon, David and Desprat, Nicolas
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 11012577-12582 (2013)

Abstract : The maintenance of cooperation in populations where public goods are equally accessible to all but inflict a fitness cost on individual producers is a long-standing puzzle of evolutionary biology. An example of such a scenario is the secretion of siderophores by bacteria into their environment to fetch soluble iron. In a planktonic culture, these molecules diffuse rapidly, such that the same concentration is experienced by all bacteria. However, on solid substrates, bacteria form dense and packed colonies that may alter the diffusion dynamics through cell-cell contact interactions. In Pseudomonas aeruginosa microcolonies growing on solid substrate, we found that the concentration of pyoverdine, a secreted iron chelator, is heterogeneous, with a maximum at the center of the colony. We quantitatively explain the formation of this gradient by local exchange between contacting cells rather than by global diffusion of pyoverdine. In addition, we show that this local trafficking modulates the growth rate of individual cells. Taken together, these data provide a physical basis that explains the stability of public goods production in packed colonies.
DOI
18
COPI buds 60-nm lipid droplets from reconstituted water-phospholipid-triacylglyceride interfaces, suggesting a tension clamp function - Thiam, Abdou Rachid and Antonny, Bruno and Wang, Jing and Delacotte, Jerome and Wilfling, Florian and Walther, Tobias C. and Beck, Rainer and Rothman, James E. and Pincet, Frederic
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 11013244-13249 (2013)

Abstract : Intracellular trafficking between organelles is achieved by coat protein complexes, coat protomers, that bud vesicles from bilayer membranes. Lipid droplets are protected by a monolayer and thus seem unsuitable targets for coatomers. Unexpectedly, coat protein complex I (COPI) is required for lipid droplet targeting of some proteins, suggesting a possible direct interaction between COPI and lipid droplets. Here, we find that COPI coat components can bud 60-nm triacylglycerol nanodroplets from artificial lipid droplet (LD) interfaces. This budding decreases phospholipid packing of the monolayer decorating the mother LD. As a result, hydrophobic triacylglycerol molecules become more exposed to the aqueous environment, increasing LD surface tension. In vivo, this surface tension increase may prime lipid droplets for reactions with neighboring proteins or membranes. It provides a mechanism fundamentally different from transport vesicle formation by COPI, likely responsible for the diverse lipid droplet phenotypes associated with depletion of COPI subunits.
 
2012
DOI
19
Statistical mechanics for natural flocks of birds - Bialek, William and Cavagna, Andrea and Giardina, Irene and Mora, Thierry and Silvestri, Edmondo and Viale, Massimiliano and Walczak, Aleksandra M.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1094786-4791 (2012)

Abstract : Flocking is a typical example of emergent collective behavior, where interactions between individuals produce collective patterns on the large scale. Here we show how a quantitative microscopic theory for directional ordering in a flock can be derived directly from field data. We construct the minimally structured (maximum entropy) model consistent with experimental correlations in large flocks of starlings. The maximum entropy model shows that local, pairwise interactions between birds are sufficient to correctly predict the propagation of order throughout entire flocks of starlings, with no free parameters. We also find that the number of interacting neighbors is independent of flock density, confirming that interactions are ruled by topological rather than metric distance. Finally, by comparing flocks of different sizes, the model correctly accounts for the observed scale invariance of long-range correlations among the fluctuations in flight direction.
DOI
20
Allosteric inhibition of individual enzyme molecules trapped in lipid vesicles - Piwonski, Hubert M. and Goomanovsky, Mila and Bensimon, David and Horovitz, Amnon and Haran, Gilad
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109E1437-E1443 (2012)

Abstract : Enzymatic inhibition by product molecules is an important and widespread phenomenon. We describe an approach to study product inhibition at the single-molecule level. Individual HRP molecules are trapped within surface-tethered lipid vesicles, and their reaction with a fluorogenic substrate is probed. While the substrate readily penetrates into the vesicles, the charged product (resorufin) gets trapped and accumulates inside the vesicles. Surprisingly, individual enzyme molecules are found to stall when a few tens of product molecules accumulate. Bulk enzymology experiments verify that the enzyme is noncompetitively inhibited by resorufin. The initial reaction velocity of individual enzyme molecules and the number of product molecules required for their complete inhibition are broadly distributed and dynamically disordered. The two seemingly unrelated parameters, however, are found to be substantially correlated with each other in each enzyme molecule and over long times. These results suggest that, as a way to counter disorder, enzymes have evolved the means to correlate fluctuations at structurally distinct functional sites.