Influence of the volume fraction on the electrokinetic properties of maghemite nanoparticles in suspension

Special issue in Honour of Pierre TURQInternational audienceWe used several complementary experimental and theoretical tools to characterise the charge properties of well-definedmaghemite nanoparticles in solution as a function of the volume fraction. The radius of the nanoparticles is equal to 6 nm.The structural charge was measured from chemical titration and was found high enough to expect some counterions tobe electrostatically attracted to the surface, decreasing the apparent charge of the nanoparticle. Direct-current conductivitymeasurements were interpreted by an analytical transport theory to deduce the value of this apparent charge, denoted here by‘dynamic effective charge’. This dynamic effective charge is found to decrease strongly with the volume fraction. In contrast,the ‘static’ effective charge, defined thanks to the Bjerrum criterion and computed from Monte Carlo simulations turns outto be almost independent of the volume fraction. In the range of Debye screening length and volume fraction investigatedhere, double layers around nanoparticles actually interact with each other. This strong interaction between nanocolloidalmaghemite particles is probably responsible for the experimental dependence of the electrokinetic properties with the volumefraction

Poisson-Boltzmann for oppositely charged bodies: an explicit derivation

The interaction between charged bodies in an ionic solution is a general problem in colloid physics and becomes a central topic in the study of biological systems where the electrostatic interaction between proteins, nucleic acids, membranes is involved. This problem is often described starting from the simple one-dimensional model of two parallel charged plates. Several different approaches to this problem exist, focusing on different features. In many cases, an intuitive expression of the pressure exerted on the plates is proposed, which includes an electrostatic plus an osmotic contribution. We present an explicit and self-consistent derivation of this formula for the general case of any charge densities on the plates and any salt solution, obtained in the framework of the Poisson-Boltzmann theory. We also show that, depending on external constraints, the correct thermodynamic potential can differ from the usual PB free energy. The resulting expression predicts, for asymmetric, oppositely charged plates, the existence of a non trivial equilibrium position with the plates separated by a finite distance. It is therefore crucial, in order to study the kinetic stability of the corresponding energy minimum, to obtain its explicit dependence on the plates charge densities and on the ion concentration. An analytic expression for the position and value of the corresponding energy minimum has been derived in 1975 by Ohshima [Ohshima H., Colloid and Polymer Sci. 253, 150-157 (1975)] but, surprisingly, this important result seems to be overlooked today. We retrieve the expressions obtained by Ohshima in a simpler formalism, more familiar to the physics community, and give a physical interpretation of the observed behavior.Comment: 11 pages, 7 figures, submitted to Molecular Physic

Extreme genetic fragility of the HIV-1 capsid

Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency >3%, and were also present in the mutant library, had fitness levels that were >40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies

Trivalent live attenuated influenza-simian immunodeficiency virus vaccines: efficacy and evolution of cytotoxic T lymphocyte escape in macaques.

There is an urgent need for a human immunodeficiency virus (HIV) vaccine that induces robust mucosal immunity. CD8+ cytotoxic T lymphocytes (CTLs) apply substantial antiviral pressure, but CTLs to individual epitopes select for immune escape variants in both HIV in humans and SIV in macaques. Inducing multiple simian immunodeficiency virus (SIV)-specific CTLs may assist in controlling viremia. We vaccinated 10 Mane-A1*08401+ female pigtail macaques with recombinant influenza viruses expressing three Mane-A1*08401-restricted SIV-specific CTL epitopes and subsequently challenged the animals, along with five controls, intravaginally with SIVmac251. Seroconversion to the influenza virus vector resulted and small, but detectable, SIV-specific CTL responses were induced. There was a boost in CTL responses after challenge but no protection from high-level viremia or CD4 depletion was observed. All three CTL epitopes underwent a coordinated pattern of immune escape during early SIV infection. CTL escape was more rapid in the vaccinees than in the controls at the more dominant CTL epitopes. Although CTL escape can incur a &quot;fitness&quot; cost to the virus, a putative compensatory mutation 20 amino acids upstream from an immunodominant Gag CTL epitope also evolved soon after the primary CTL escape mutation. We conclude that vaccines based only on CTL epitopes will likely be undermined by rapid evolution of both CTL escape and compensatory mutations. More potent and possibly broader immune responses may be required to protect pigtail macaques from SIV. <br /

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Influence of recombination on acquisition and reversion of immune escape and compensatory mutations in HIV-1

AbstractFollowing transmission, HIV-1 adapts in the new host by acquiring mutations that allow it to escape from the host immune response at multiple epitopes. It also reverts mutations associated with epitopes targeted in the transmitting host but not in the new host. Moreover, escape mutations are often associated with additional compensatory mutations that partially recover fitness costs. It is unclear whether recombination expedites this process of multi-locus adaptation. To elucidate the role of recombination, we constructed a detailed population dynamics model that integrates viral dynamics, host immune response at multiple epitopes through cytotoxic T lymphocytes, and viral evolution driven by mutation, recombination, and selection. Using this model, we compute the expected waiting time until the emergence of the strain that has gained escape and compensatory mutations against the new host's immune response, and reverted these mutations at epitopes no longer targeted. We find that depending on the underlying fitness landscape, shaped by both costs and benefits of mutations, adaptation proceeds via distinct dominant pathways with different effects of recombination, in particular distinguishing escape and reversion. When adaptation at a single epitope is involved, recombination can substantially accelerate immune escape but minimally affects reversion. When multiple epitopes are involved, recombination can accelerate or inhibit adaptation depending on the fitness landscape. Specifically, recombination tends to delay adaptation when a purely uphill fitness landscape is accessible at each epitope, and accelerate it when a fitness valley is associated with each epitope. Our study points to the importance of recombination in shaping the adaptation of HIV-1 following its transmission to new hosts, a process central to T cell-based vaccine strategies

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Potential syndromes linking dispersal and reproduction in the hermaphrodite land snail \textitCornu aspersum

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