Squeezing Protein Shells: How Continuum Elastic Models, Molecular Dynamics Simulations, and Experiments Coalesce at the Nanoscale

The current rapid growth in the use of nanosized particles is fueled in part by our increased understanding of their physical properties and ability to manipulate them, which is essential for achieving optimal functionality. Here we report detailed quantitative measurements of the mechanical response of nanosized protein shells (viral capsids) to large-scale physical deformations and compare them with theoretical descriptions from continuum elastic modeling and molecular dynamics (MD). Specifically, we used nanoindentation by atomic force microscopy to investigate the complex elastic behavior of Hepatitis B virus capsids. These capsids are hollow, ∼30 nm in diameter, and conform to icosahedral (5-3-2) symmetry. First we show that their indentation behavior, which is symmetry-axis-dependent, cannot be reproduced by a simple model based on Föppl-von Kármán thin-shell elasticity with the fivefold vertices acting as prestressed disclinations. However, we can properly describe the measured nonlinear elastic and orientation-dependent force response with a three-dimensional, topographically detailed, finite-element model. Next, we show that coarse-grained MD simulations also yield good agreement with our nanoindentation measurements, even without any fitting of force-field parameters in the MD model. This study demonstrates that the material properties of viral nanoparticles can be correctly described by both modeling approaches. At the same time, we show that even for large deformations, it suffices to approximate the mechanical behavior of nanosized viral shells with a continuum approach, and ignore specific molecular interactions. This experimental validation of continuum elastic theory provides an example of a situation in which rules of macroscopic physics can apply to nanoscale molecular assemblies

Hiv-1 Gp41 And Gp160 Are Hyperthermostable Proteins In A Mesophilic Environment - Characterization Of Gp41 Mutants

HIV gp41(24-157) unfolds cooperatively over the pH range of 1.0-4.0 with T(m) values of > 100 degrees C. At pH 2.8, protein unfolding was 80% reversible and the DeltaH(vH)/DeltaH(cal) ratio of 3.7 is indicative of gp41 being trimeric. No evidence for a monomer-trimer equilibrium in the concentration range of 0.3-36 micro m was obtained by DSC and tryptophan fluorescence. Glycosylation of gp41 was found to have only a marginal impact on the thermal stability. Reduction of the disulfide bond or mutation of both cysteine residues had only a marginal impact on protein stability. There was no cooperative unfolding event in the DSC thermogram of gp160 in NaCl/P(i), pH 7.4, over a temperature range of 8-129 degrees C. When the pH was lowered to 5.5-3.4, a single unfolding event at around 120 degrees C was noted, and three unfolding events at 93.3, 106.4 and 111.8 degrees C were observed at pH 2.8. Differences between gp41 and gp160, and hyperthermostable proteins from thermophile organisms are discussed. A series of gp41 mutants containing single, double, triple or quadruple point mutations were analysed by DSC and CD. The impact of mutations on the protein structure, in the context of generating a gp41 based vaccine antigen that resembles a fusion intermediate state, is discussed. A gp41 mutant, in which three hydrophobic amino acids in the gp41 loop were replaced with charged residues, showed an increased solubility at neutral pH

Síndrome da dilatação volvo gástrica em cães Gastric volvulus dilatation syndrome in dogs

A síndrome da dilatação volvo gástrica (DVG) é uma condição grave, de caráter agudo, que confere alto índice de óbito em pequenos animais. A etiologia não está completamente estabelecida e, em contrapartida, diversas possibilidades de tratamento são descritas. A DVG causa grave redução na perfusão tecidual, afetando vários órgãos, incluindo os sistemas respiratório e cardiovascular. Este estudo tem como objetivo realizar uma revisão de literatura sobre a patogenia desta síndrome e seu tratamento.<br>The syndrome of gastric dilatation volvulus (GDV) is a severe condition of acute character, which gives a high rate of death in small animals. The etiology is not fully established, however, several treatment options have been described. The DVG causes severe reduction in tissue perfusion, affecting many organs, including the respiratory and cardiovascular systems. This study aims to conduct a comprehensive literature review of the pathogenesis of this syndrome as well as its treatment