Publications

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1. •Stiffness heterogeneity of small viral capsids
   

2. L. Menou, Y. Carrasco Salas, L. Lecoq, A. Salvetti, C. Faivre-Moskalenko, M. Castelnovo; Phys. Rev. E, 2021, 104, 064408.
   

Abstract: Nanoindentation of viral capsids provides an efficient tool in order to probe their elastic properties. We investigate in the present work the various sources of stiffness heterogeneity as observed in atomic force microscopy experiments. By combining experimental results with both numerical and analytical modeling, we first show that for small viruses, a position-dependent stiffness is observed. This effect is strong and has not been properly taken into account previously. Moreover, we show that a geometrical model is able to reproduce this effect quantitatively. Our work suggests alternative ways of measuring stiffness heterogeneities on small viral capsids. This is illustrated on two different viral capsids: Adeno associated virus serotype 8 (AAV8) and hepatitis B virus (HBV with T = 4). We discuss our results in light of continuous elasticity modeling.

1. •Mechanical stress relaxation in molecular self-assembly
   

2. L. Menou, M. Castelnovo; Soft Matter, 2019, 15, 6180.
   

Abstract: Molecular self-assembly on a curved substrate leads to the spontaneous inclusion of topological defects in the growing bidimensional crystal, unlike assembly on a flat substrate. We propose in this work a quantitative mechanism for this phenomenon by using standard thin shell elasticity. The Gaussian curvature of the substrate induces large in-plane compressive stress as the surface grows, in particular at the rim of the assembly, and the addition of a single defect relaxes this mechanical stress. We found out that the value of azimuthal stress at the rim of the assembly determines the preferred directions for defect nucleation. These results are also discussed as a function of different defect combinations, like dislocations and grain boundaries or scars. In particular, the elastic model permits us to compare quantitatively the ability of various defects to relax mechanical stress. Moreover, these findings allow us to understand the progressive building-up of the typical disclination and grain boundary pattern observed for ground states of large 2D spherical crystals.

1. •Characterization of AAV vector particle stability at the single capsid level
   

2. J. Bernaud, A. Rossi, L. Gardette, L. Aillot, H. Buning, M. Castelnovo, A. Salvetti, C. Faivre-Moskalenko; J. Biol. Phys., 2018, 44, 181.
   

Abstract: Virus families have evolved different strategies for genome uncoating, which are also followed by recombinant vectors. Vectors derived from adeno-associated viruses (AAV) are considered as leading delivery tools for in vivo gene transfer, and in particular gene therapy. Using a combination of atomic force microscopy (AFM), biochemical experiments, and physical modeling, we investigated here the physical properties and stability of AAV vector particles. We first compared the morphological properties of AAV vectors derived from two different serotypes (AAV8 and AAV9). Furthermore, we triggered ssDNA uncoating by incubating vector particles to increasing controlled temperatures. Our analyses, performed at the single-particle level, indicate that genome release can occur in vitro via two alternative pathways: either the capsid remains intact and ejects linearly the ssDNA molecule, or the capsid is ruptured, leaving ssDNA in a compact entangled conformation. The analysis of the length distributions of ejected genomes further revealed a two-step ejection behavior. We propose a kinetic model aimed at quantitatively describing the evolution of capsids and genomes along the different pathways, as a function of time and temperature. This model allows quantifying the relative stability of AAV8 and AAV9 particles.

1. •Viral self-assembly pathway and mechanical stress relaxation
   

2. M. Castelnovo; Phys. Rev. E, 2017, 95, 052405.
   

Abstract: The final shape of a virus is dictated by the self-assembly pathway of its constituents. Using standard thin-shell elasticity, we highlight the prominent role of the viral shell’s spontaneous curvature in determining the assembly pathway. In particular, we demonstrate that the mechanical stress inherent to the growth of a curved surface can be relaxed in two different ways in the early steps of assembly, depending on the value of the spontaneous curvature of the surface. This important result explains why most viral shells have either a compact shape with icosahedral symmetry or an elongated shape lacking this symmetry.

1. •Assemblage et désassemblage des virus: mode d’emploi
   

2. G. Tresset, M. Castelnovo, A. Leforestier; Reflets de la physique, 2017, 52, 22.
   

Abstract: Les virus biologiques sontdes entités fascinantes qui opposent une relative simplicité dans leur structure à une surprenante sophistication dans leur fonction. Bien qu’inertes, leurs centaines voire milliers de composants moléculaires s’assemblent et se désassemblent spontanément dans un milieu cellulaire hétérogène et encombré, avec une précision quasi-atomique et un taux d’erreur marginal.

Les concepts théoriques et expérimentaux de la physique statistique et des fluides complexes permettent aujourd’huide décrire la thermodynamique et les phénomènes hors équilibre qui régissent l’assemblage et le désassemblage de virus naturels ou synthétiques.

1. •Single particle maximum likelihood reconstruction from superresolution microscopy images
   

2. T. Verdier, J. Gunzenhauser, S. Manley, M. Castelnovo; PLoS One, 2017, 12, e0172943.
   

Abstract: Point localization superresolution microscopy enables fluorescently tagged molecules to be imaged beyond the optical diffraction limit, reaching single molecule localization precisions down to a few nanometers.  For small objects whose sizes are few times this precision, localization uncertainty prevents the straightforward extraction of a structural model from the reconstructed images. We demonstrate in the present work that this limitation can be overcome at the single particle level, requiring no particle averaging, by using a maximum likelihood reconstruction (MLR) method perfectly suited to the stochastic nature of such superresolution imaging. We validate this method by extracting structural information from both simulated and experimental PALM data of immature virus-like particles of the Human Immunodeficiency Virus (HIV-1). MLR allows us to measure  the radii of individual viruses with precision of a few nanometers and confirms the incomplete closure of the viral protein lattice. The quantitative results of our analysis are consistent with previous cryoelectron microscopy characterizations. Our study establishes the framework for a method that can  be broadly applied to PALM data to determine the structural parameters for an existing structural model, and is particularly well suited to heterogeneous features due to its single particle implementation.

1. •Modeling the kinetics of open self-assembly
   

2. T. Verdier, L. Foret, M. Castelnovo; J. Phys Chem B, 2016, 120, 26, 6411.
   

Abstract: In this work, we explore theoretically the kinetics of molecular self-assembly in the presence of constant monomer flux as an input, and a maximal size. The proposed model is supposed to reproduce the dynamics of viral self-assembly for envelopped virus. Our results show that the convergence towards the stationary state is reached through assembly waves. Interestingly, we show that the production of complete clusters is much more efficient in the presence of a constant input flux, rather than providing all monomers at the beginning of the self-assembly.

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1. •Atomic force microscopy
   

2. Bernaud J., Castelnovo M., Muriaux D.,  Faivre-Moskalenko C.; M.S. - Medecine sciences , 2015, 31, 522.
   

Abstract: Each step of the HIV-1 life cycle frequently involves a change in the morphology and/or mechanical properties of the viral particle or core. The atomic force microscope (AFM) constitutes a powerful tool for characterizing these physical changes at the scale of a single virus. Indeed, AFM enables the visualization of viral capsids in a controlled physiological environment and to probe their mechanical properties by nano-indentation. Finally, AFM force spectroscopy allows to characterize the affinities between viral envelope proteins and cell receptors at the single molecule level.

1. •Dynamical DNA accessibility induced by chromatin remodeling and protein binding
   

2. Montel F., Faivre-Moskalenko C.,  Castelnovo M., ; Phys. Rev. E , 2014, 90, 052717.
   

Abstract: Chromatin remodeling factors are enzymes being able to alter locally chromatin structure at the nucleosomal level and they actively participate in the regulation of gene expression. Using simple rules for individual nucleosome motion induced by a remodeling factor, we designed simulations of the remodeling of oligomeric chromatin, in order to address quantitatively collective effects in DNA accessibility upon nucleosome mobilization. Our results suggest that accessibility profiles are inhomogeneous thanks to borders effects like protein binding. Remarkably, we show that the accessibility lifetime of DNA sequence is roughly doubled in the vicinity of borders as compared to its value in bulk regions far from the borders. These results are quantitatively interpreted as resulting from the confined diffusion of a large nucleosome depleted region.

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2. •Comparing open and closed molecular self-assembly
   

3. Castelnovo M., Verdier T., Foret L.; Europhys. Lett. , 2014, 105, 28006.
   

Abstract: We study theoretically in the present work the self-assembly of molecules in an open system, which is fed by monomers and depleted in partial or complete clusters. Such a scenario is likely to occur for example in the context of viral self-assembly. We provide a general formula for the mean-field size distribution which is valid both at equilibrium in a closed system, and in the stationary state in an open system. This allows us to explore in a simple way out-of-equilibrium features for self-assembly and compare them to equilibrium properties. In particular, we identify a region of parameter space for which the out-of-equilibrium size distribution in the presence of external fluxes is equal to the equilibrium size distribution in the absence of external fluxes, up to a constant renormalization factor. The range of validity of this result and its consequences are discussed.

1. •RNA control of HIV-1 particle size polydispersity
   

2. Faivre-Moskalenko, C., Thomas A.,  Tartour K., Bernaud J., Beck Y., Iazykov M., Danial J., Lourdin M., Muriaux D.,  Castelnovo M.; PLoS One 2014, 9, e83874.
   

Abstract: HIV-1, an enveloped RNA virus, produces viral particles that are known to be much more heterogeneous in size than the one of non-enveloped viruses. We present here a novel strategy to study HIV-1 Viral Like Particles (VLP) assembly by measuring the size distribution of these purified VLP and subsequent viral cores thanks to Atomic Force Microscopy imaging and statistical analysis. This strategy allowed us to identify whether the presence or the absence of viral RNA acts as a modulator for VLP and cores size heterogeneity in a large population of particles. These results are analyzed in the light of statistical physics of the self- assembly process. In particular, our results reveal that the modulation of size distribution by the presence of viral RNA, or its absence, is qualitatively reproduced within this model, and is essentially an entropic effect associated to the modulation of RNA uptake by the nascent
VLP .

1. •Entropic control of particle size during viral self-assembly
   

2. Castelnovo M., Muriaux D., Faivre-Moskalenko C.; New Journal of Physics , 2013, 15, 035028.
   

Abstract: Morphologic diversity is observed across all families of viruses. Yet these supra-molecular assemblies are produced most of the time in a spontaneous way through complex molecular self-assembly scenarios. The modeling of these phenomena remains a challenging problem within the emerging field of Physical Virology. We present in this work a theoretical analysis aiming at highlighting the particular role of configuration entropy in the control of viral particle size distribution. Specializing this model to retroviruses like HIV-1, we predict a new mechanism of entropic control of both RNA uptake into the viral particle, and of the particle’s size distribution. Evidence of this peculiar behavior has been recently reported experimentally.

1. •Challenging packaging limits and infectivity of phage lambda
   

2. Nurmemmedov E, Castelnovo M., Medina E., Catalano CE., Evilevitch. A; J. Mol. Biol. , 2012, 415,263-273.
   

Abstract: The terminase motors of bacteriophages have been shown to be among the strongest active machines in the biomolecular world, being able to package several tens of kilobase pairs of viral genome into a capsid within minutes. Yet these motors are hindered at the end of the packaging process by the progressive build-up of a force resisting packaging associated with already packaged DNA. In this experimental work, we raise the issue of what sets the upper limit on the length of the genome that can be packaged by the terminase motor of phage λ and still yield infectious virions, and the conditions under which this can be efficiently performed. Using a packaging strategy developed in our laboratory of building phage λ from scratch, together with plaque assay monitoring, we have been able to show that the terminase motor of phage λ is able to produce infectious particles with up to 110% of the wild-type (WT) λ-DNA length. However, the phage production rate, and thus the infectivity, decreased exponentially with increasing DNA length, and was a factor of 103 lower for the 110% λ-DNA phage. Interestingly, our in vitro strategy was still efficient in fully packaging phages with DNA lengths as high as 114% of the WT length, but these viruses were unable to infect bacterial cells efficiently. Further, we demonstrated that the phage production rate is modulated by the presence of multivalent ionic species. The biological consequences of these finding are discussed.

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2. •RSC remodeling of oligo-nucleosomes: an atomic force microscopy study; Montel F., Castelnovo M., Menoni H., Angelov D., Dimitrov S., Faivre-Moskalenko C. ; Nuc. Ac. Research. , 2011, 39, 2571-2579.
   

Abstract: RSC is an essential chromatin remodeling factor that is required for the control of several processes including transcription, repair and replication. The ability of RSC to relocate centrally positioned mononucleosomes at the end of nucleosomal DNA is firmly established, but the data on RSC action on oligo-nucleosomal templates remains still scarce. By using Atomic Force Microscopy (AFM) imaging, we have quantitatively studied the RSC- induced mobilization of positioned di- and trinucleosomes as well as the directionality of mobilization on mononucleosomal template labeled at one end with streptavidin. AFM imaging showed only a limited set of distinct configurational states for the remodeling products. No stepwise or preferred directionality of the nucleosome motion was observed. Analysis of the corresponding reaction pathways allows deciphering the mechanistic features of RSC-induced nucleosome relocation. The final outcome of RSC remodeling of oligosome templates is the packing of the nucleosomes at the edge of the template, providing large stretches of DNA depleted of nucleosomes. This feature of RSC may be used by the cell to overcome the barrier imposed by the presence of nucleosomes.

1. •DNA heats up: Energetics of genome ejection from phage revealed by isothermal titration calorimetry ; Jeembaeva M., Jonnson B., Castelnovo M., Evilevitch A. ; J. Mol. Biol. , 2010, 395, 1079-1087.
   

Abstract: Most bacteriophages are known to inject their double-stranded DNA into bacteria upon receptor binding in an essentially spontaneous way. This downhill thermodynamic process from the intact virion toward the empty viral capsid plus released DNA is made possible by the energy stored during active packaging of the genome into the capsid. Only indirect measurements of this energy have been available until now using either single-molecule or osmotic suppression techniques. In this paper, we describe for the first time the use of isothermal titration calorimetry to directly measure the heat released (or equivalently the enthalpy) during DNA ejection from phage lambda, triggered in solution by a solubilized receptor. Quantitative analysis of the results lead to the identification of thermodynamic determinants associated to DNA ejection. The values obtained were found to be consistent with those previously predicted by analytical models and numerical simulations. Moreover, the results confirm the role of DNA hydration in the energetics of genome confinement in viral capsids.

1. •The dynamics of individual nucleosomes controls the chromatin condensation pathway: direct AFM visualization of variant chromatin; Montel F., Menoni H., Castelnovo M., Bednar J., Dimitrov S., Angelov A., Faivre-Moskalenko C. ; Biophys. J. , 2009 ,97, 544-553.
   

Abstract: Chromatin organization and dynamics is studied in this work at scales ranging from single nucleosome to nucleosomal array by using a unique combination of biochemical assays, single molecule imaging technique and numerical modeling. We demonstrate that a subtle modification in the nucleosome structure induced by the histone variant H2A.Bbd drastically modifies the higher order organization of the nucleosomal arrays. Importantly, as directly visualized by AFM, conventional H2A nucleosomal arrays exhibit specific local organization,in contrast to H2A.Bbd arrays, which show "beads on a string" structure. The combination of systematic image analysis and theoretical modeling allows a quantitative description relating the observed gross structural changes of the arrays to their local organization. Our results strongly suggest that higher-order organization of H1-free nucleosomal arrays is mainly determined by the fluctuation properties of individual nucleosomes. Moreover, numerical simulations suggest the existence of attractive interactions between nucleosomes to provide the degree of compaction observed for conventional chromatin fibers.

1. •Osmotic pressure: resisting or promoting DNA ejection from phage? Jeembaeva M., Castelnovo M., Larsson F., Evilevitch A. ; J. Mol. Biol. , 2008 , 381,  310-323.
   

Abstract: Recent in vitro experiments have shown that DNA ejection from bacteriophage can be partially stopped by surrounding osmotic pressure when ejected DNA is digested by DNAse I on the course of ejection. We argue in this work  by combination of experimental techniques (osmotic suppression without DNAse I monitored by UV absorbance, pulse-field electrophoresis, and cryo-EM visualization) and simple scaling modeling that intact genome (i.e. undigested) ejection in a crowded environment is, on the contrary, enhanced or eventually complete with the help of a pulling force resulting from DNA condensation induced by the osmotic stress itself. This demonstrates that in vivo, the osmotically stressed cell cytoplasm will promote phage DNA ejection rather than resisting it. The further addition of DNA-binding proteins under crowding conditions is shown to enhance the extent of ejection. We also found some optimal crowding conditions for which DNA content remaining in the capsid upon ejection is maximum, which correlates well with the optimal conditions of maximum DNA packaging efficiency into viral capsids observed almost 20 years ago. Biological consequences of this finding are discussed.

1. •Effects of salt concentrations and bending energy on the extent of ejection of phage genomes; Evilevitch A., Fang L. T., Yoffe A., Castelnovo M., Rau D. C., Parsegian A. V., Gelbart W. M., Knobler C. M. ; Biophys. J. , 2008 , 94, 1110-1120.
   

Abstract: Recent work has shown that pressures inside dsDNA phage capsids can be as high as many tens of atmospheres; it is this pressure that is responsible for initiation of the delivery of phage genomes to host cells. The forces driving ejection of the genome have been shown to decrease monotonically as ejection proceeds, and hence to be strongly dependent on the genome length. Here we investigate the effects of ambient salts on the pressures inside phage lambda, for the cases of mono-, di-, and tetra-valent cations and measure how the extent of ejection against a fixed osmotic pressure (mimicking the bacterial cytoplasm) varies with cation concentration. We find, for example, that the ejection fraction is halved upon the addition of 30 mM Mg2+ and is decreased by a factor of ten upon addition of 1mM spermine. These effects are calculated from a simple model of genome packaging, using DNA-DNA repulsion energies as determined independently from X-ray diffraction measurements on bulk DNA solutions. By comparing the measured ejection fractions with values implied from the bulk DNA solution data, we predict that the bending energy makes the d-spacings inside the capsid larger than those for bulk DNA at the same osmotic pressure.

1. •Biophysics of viral infectivity: matching genome length with capsid size;   Nurmemmedov, E.; Castelnovo, M. ;Catalano , C.E.; Evilevitch A., ; Quart. Rev. Biophysics , 2007 , 40, 327-356.
   

Abstract: In this review, we discuss recent advances in biophysical virology, presenting experimental and theoretical studies on the physical properties of viruses. We focus on the double-stranded (ds) DNA bacteriophages as model systems for all of the dsDNA viruses both prokaryotic and eukaryotic. Recent studies demonstrate that the DNA packaged into viral capsid is highly pressurized, which provides a force for the first step of passive injection of viral DNA into a bacterial cell. Moreover, specific studies on capsid strength show a strong correlation between genome length and capsid size and robustness. The implications of these newly appreciated physical properties of a viral particle with respect to the infection process are discussed.

1. •DNA ejection from bacteriophage: towards a general behavior for osmotic-supression experiments, Castelnovo, M.;Evilevitch A. ; Eur. Phys. J. E , 2007 , 24, 9-18.
   

Abstract: We present in this work in vitro measurements of the force ejecting DNA from two distinct bacteriophages (T5 and λ) using the osmotic-suppression technique. Our data are analyzed by revisiting the current theories of DNA packaging in spherical capsids. In particular we show that a simplified analytical model based on bending considerations only is able to account quantitatively for the experimental findings. Physical and biological consequences are discussed.

1. •AFM Imaging of SWI/SNF action: mapping the nucleosome remodeling and sliding; Montel F., Fontaine E., Saint-Jean P., Castelnovo, M.; Moskalenko-Faivre C. Biophys. J., 2007 , 93, 566-578.
   

Abstract: We propose a combined experimental (Atomic Force Microscopy) and theoretical study of the structural and dynamical properties of nucleosomes. In contrast to biochemical approaches, this method allows to determine simultaneously the DNA complexed length distribution and nucleosome position in various contexts. First, we show that differences in the nucleo-proteic structure observed between conventional H2A and H2A.Bbd variant nucleosomes induce quantitative changes in the in the length distribution of DNA complexed with histones. Then, the sliding action of remodeling complex SWI/SNF is characterized through the evolution of the nucleosome position and wrapped DNA length mapping. Using a linear energetic modelfor the distribution of DNA complexed length, we extract the net wrapping energy of DNA onto the histone octamer, and compare it to previous studies.

1. •Electrophoresis of positioned nucleosomes; Castelnovo, M.; Grauwin S.; Biophys. J., 2007, 92, 3022-3031.
   

Abstract: We present in this paper an original approach to compute the electrophoretic mobility of rigid nucleo-protein complexes like nucleosomes. This model allows to address theoretically the influence of complex position along DNA, as well as wrapped length of DNA on the electrophoretic mobility of the complex. The predictions of the model are in qualitative agreement with experimental results on mononucleosomes assembled on short DNA fragments (<400bp). Influence of additional experimental parameters like gel concentration, ionic strength, effective charges is also discussed in the framework of the model, and is found to be qualitatively consistent with experiments when available. Based on the present model, we propose a simple semi-empirical formula describing positioning of nucleosomes as seen through electrophoresis.

1. •Binding effects in multivalent Gibbs-Donnan equilibrium; Castelnovo, M.; Evilevitch, A.; Europhys. Lett., 2006, 73, 635-642.
   

Abstract: The classical Gibbs-Donnan equilibrium describes excess osmotic pressure associated with confined colloidal charges embedded in an electrolyte solution. In this work, we extend this approach to describe the influence of multivalent ion binding on the equilibrium force acting on a charged rod translocating between two compartments, thereby mimicking ionic effects on force balance during in vitro DNA ejection from bacteriophage. The subtle interplay between Gibbs-Donnan equilibrium and adsorption equilibrium leads to a non-monotonic variation of the ejection force as multivalent salt concentration is increased, in qualitative agreement with experimental observations.

1. •Measuring the Force Ejecting DNA from Phage; Evilevitch, A.; Castelnovo, M.; Knobler, C.M.; Gelbart, W.M. J. Phys. Chem. B, 2004, 108(21), 6838-6843.
   

Abstract: We discuss how a balance can be established between the force acting to eject DNA from viral capsids and the force resisting its entry into a colloidal suspension that mimics the host cell cytoplasm. The ejection force arises from the energy stored in the capsid as a consequence of the viral genome (double-stranded DNA) being strongly bent and crowded on itself. The resisting force is associated with the osmotic pressure exerted by the colloidal particles in the host solution. Indeed, recent experimental work has demonstrated that the extent of ejection can be progressively limited by increasing the external osmotic pressure; at a sufficiently high pressure, the ejection is completely suppressed. We outline here a theoretical analysis that allows a determination of the internal (capsid) pressure by examining the different relations between force and pressure inside and outside the capsid using the experimentally measured position of the force balance.

1. •Semiflexible Chain Condensation by Neutral Depleting Agents: Role of Correlations between Depletants;  Castelnovo, M.; Gelbart, W. M.; Macromolecules,2004, 37(9), 3510-3517.
   

Abstract: We revisit the problem of semiflexible chain condensation by neutral depleting agents (e.g., colloidal spheres or flexible polymers) by using a simple formalism that allows us to address its main features without specifying the kind of depleting agents. Correlations between depleting agents are shown to produce a reswelling of the chain at high enough volume fraction, consistent with an earlier analysis by Grosberg et al. [Biopolymers 1982, 21, 2413] in the context of DNA condensation induced by neutral polymers. It is also shown that the conditions under which spherical colloids can condense a semiflexible chain are strongly restrictive, unlike what has been recently claimed. The formalism allows us to compare the efficiency of colloids vs polymers as condensing agents.

1. •Thermodynamics of Micellization of Oppositely Charged Polymers; Castelnovo, M. ; Europhysics Letters, 2003, 62 (6), 841-847.
   

Abstract: The complexation of oppositely charged colloidal objects is considered in this paper as a thermodynamic micellization process where each kind of object needs the others to micellize. This requirement gives rise to quantitatively different behaviors than the so-called mixed-micellization where each species can micellize separately. A simple model of the grand potential for micelles is proposed to corroborate the predictions of this general approach.

1. •Osmotic Force Resisting Chain Insertion in a Colloidal Suspension, Castelnovo, M.; Bowles, R.K.; Reiss, H; Gelbart ,W.M. ;  European Physical Journal E, 2003, 10(2):,191-197.
   

Abstract :We consider the problem of inserting a stiff chain into a colloidal suspension of particles that interact with it through excluded volume forces. The free energy of insertion is associated with the work of creating a cavity devoid of colloid and sufficiently large to accommodate the chain. The corresponding work per unit length is the force that resists the entry of the chain into the colloidal suspension. In the case of a hard sphere fluid, this work can be calculated straightforwardly within the scaled particle theory; for solutions of flexible polymers, on the other hand, we employ simple scaling arguments. The forces computed in these ways are shown, for nanometer chain and colloid diameters, to be of the order of tens of pN for solution volume fractions of a few tenths. These magnitudes are argued to be important for biophysical processes such as the ejection of DNA from viral capsids into the cell cytoplasm.

1. •Phase Diagram of Diblock Polyampholyte Solutions; Castelnovo, M; Joanny, J.F.;Macromolecules, 2002, 35(11); 4531-4538.
   

Abstract: We discuss in this paper the phase diagram of a diblock polyampholyte solution in the limit of high ionic strength as a function of concentration and charge asymmetry. This system is shown to be very similar to solutions of so-called charged-neutral diblock copolymers: at zero charge asymmetry, the solution phase separates into a polyelectrolyte complex and almost pure solvent. Above a charge asymmetry threshold, the copolymers are soluble as finite size aggregates. Scaling laws of the aggregates radius as a function of pH of the solution are in qualitative agreement with experiments.

1. •Complexation between Oppositely Charged Polyelectrolytes: Beyond the Random Phase Approximation; Castelnovo, M.; Joanny, J.F., European Physical Journal E, 2001, 6(5); 377-386.
   

Abstract: We consider the phase behavior of polymeric systems by calculating the structure factors beyond the Random Phase Approximation. The effect of this correction to the mean-field RPA structure factor is shown to be important in the case of Coulombic systems. Two examples are given: simple electrolytes and mixtures of incompatible oppositely charged polyelectrolytes. In this last case, all former studies predicted an enhancement of compatibility for increasing charge densities; we also describe the complexation transition between the polyelectrolytes. We determine a phase diagram of the polyelectrolyte mixture that includes both complexation and incompatibility.

1. •Charge Distribution on Annealed Polyelectrolytes; Castelnovo, M.; Sens, P.; Joanny, J.F. European Physical Journal E, 2000, 1(2-3); 115-125.
   

Abstract: We investigate the equilibrium charge distribution along a single annealed polyelectrolyte chain under different conditions. The coupling between the conformation of the chain and the local charge distribution is described for various solvent qualities and salt concentration. In salt free solution, we find a slight charge depletion in the central part of the chain: the charges accumulate at the ends. The effect is less important if salt is added to the solution since the charge inhomogeneity is localized close to the chain ends over a distance of order of the Debye length. In the case of poor solvent conditions we find a different charge per monomer in the beads and in the strings in the framework of the necklace model. This inhomogeneity leads to a charge instability and a first order transition between spherical globules and elongated chains.

1. •Formation of Polyelectrolyte Multilayers; Castelnovo, M.; Joanny, J.F., Langmuir, 2000, 16(19); 7524-7532.
   

Abstract: A mechanism for the formation of polyelectrolyte multilayers is proposed. All of the experiments on such systems show that there is strong interpenetration of consecutive layers. We explain the very strong stability of the multilayers by the complexation between polyelectrolytes of opposite signs. Scaling laws on bulk polyelectrolyte complexation and their applications to the case of multilayers are derived in analogy with the description of neutral polymers under poor solvent conditions. Qualitative agreement is reached with some recent experiments.

1. •Adsorption of Charged Polymers; Joanny, J.F.; Castelnovo, M.; Netz, R.R., Journal of Physics-Condensed Matter, 2000, 12(8A); A1-A7.
   

Abstract: We review some of the theoretical results that we have obtained recently on the adsorption of polyelectrolytes on surfaces of opposite charge. We consider two problems, the formation of polyelectrolyte multilayers and the formation of complexes between rigid polyelectrolytes and small spheres. For polyelectrolyte multilayers, the overcompensation of the adsorbing surface charge and the anchoring between consecutive layers are studied. For polyelectrolyte-sphere complexes, the wrapping of the polymer on the sphere is shown to occur continuously at low ionic strength and discontinuously at high ionic strength. The findings of some recent experiments are briefly compared with our results.