Anisotropic plastic deformation by viscous flow in ion tracks

A model describing the origin of ion beam-induced anisotropic plastic deformation is derived and discussed. It is based on a viscoelastic thermal spike model for viscous flow in single ion tracks derived by Trinkaus and Ryazanov. Deviatoric (shear) stresses, brought about by the rapid thermal expansion of the thermal spike, relax at ion track temperatures beyond a certain flow temperature. Shear stress relaxation is accompanied by the generation of viscous strains. The model introduces differential equations describing the time evolution of the radial and axial stresses, enabling an exact derivation of the viscous strains for any ion track temperature history T(t). It is shown that the viscous strains effectively freeze in for large track cooling rates, whereas reverse viscous flow reduces the net viscous strains in the ion track for smaller cooling rates. The model is extended to include finite-size effects that occur for ion tracks close to the sample edge, enabling a comparison with experimental results for systems with small size. The "effective flow temperature approach" that was earlier introduced by Trinkaus and Ryazanov by making use of Eshelby's theory of elastic inclusions, follows directly from the viscoelastic model as a limiting case. We show that the viscous strains in single ion tracks are the origin of the macroscopic anisotropic deformation process. The macroscopic deformation rate can be directly found by superposing the effects of single ion impacts. By taking realistic materials parameters, model calculations are performed for experimentally studied cases. Qualitative agreement is observed

Exploring Intra- and Inter-Regional Interactions in the IDP α-Synuclein Using smFRET and MD Simulations

Theoretical concepts from polymer physics are often used to describe intrinsically disordered proteins (IDPs). However, amino acid interactions within and between regions of the protein can lead to deviations from typical polymer scaling behavior and even to short-lived secondary structures. To investigate the key interactions in the dynamic IDP α-synuclein (αS) at the amino acid level, we conducted single-molecule fluorescence resonance energy transfer (smFRET) experiments and coarse-grained molecular dynamics (CG-MD) simulations. We find excellent agreement between experiments and simulations. Our results show that a physiological salt solution is a good solvent for αS and that the protein is highly dynamic throughout its entire chain, with local intra- and inter-regional interactions leading to deviations from global scaling. Specifically, we observe expansion in the C-terminal region, compaction in the NAC region, and a slightly smaller distance between the C- and N-termini than expected. Our simulations indicate that the compaction in the NAC region results from hydrophobic aliphatic contacts, mostly between valine and alanine residues, and cation−π interactions between lysine and tyrosine. In addition, hydrogen bonds also seem to contribute to the compaction of the NAC region. The expansion of the C-terminal region is due to intraregional electrostatic repulsion and increased chain stiffness from several prolines. Overall, our study demonstrates the effectiveness of combining smFRET experiments with CG-MD simulations to investigate the key interactions in highly dynamic IDPs at the amino acid level.</p

Computation of Hemagglutinin Free Energy Difference by the Confinement Method

Hemagglutinin (HA) mediates membrane fusion, a crucial step during influenza virus cell entry. How many HAs are needed for this process is still subject to debate. To aid in this discussion, the confinement free energy method was used to calculate the conformational free energy difference between the extended intermediate and postfusion state of HA. Special care was taken to comply with the general guidelines for free energy calculations, thereby obtaining convergence and demonstrating reliability of the results. The energy that one HA trimer contributes to fusion was found to be 34.2 ± 3.4<i>k</i>_B<i>T</i>, similar to the known contributions from other fusion proteins. Although computationally expensive, the technique used is a promising tool for the further energetic characterization of fusion protein mechanisms. Knowledge of the energetic contributions per protein, and of conserved residues that are crucial for fusion, aids in the development of fusion inhibitors for antiviral drugs

Flexible and Extended Linker Domains Support Efficient Targeting of Heh2 to the Inner Nuclear Membrane

The nuclear pore complex (NPC) is embedded in the nuclear envelope and forms the main gateway to the nuclear interior including the inner nuclear membrane (INM). Two INM proteins in yeast are selectively imported. Their sorting signals consist of a nuclear localization signal, separated from the transmembrane domain by a long intrinsically disordered (ID) linker. We used computational models to predict the dynamic conformations of ID linkers and analyzed the INM targeting efficiency of proteins with linker regions with altered Stokes radii and decreased flexibilities. We find that flexibility, Stokes radius, and the frequency at which the linkers are at an extended end-to-end distance larger than 25 nm are good predictors for the targeting of the proteins. The data are consistent with a transport mechanism in which INM targeting of Heh2 is dependent on an ID linker that facilitates the crossing of the approximately 25-nm thick NPC scaffold

Modelling Semiosis of Design

This paper addresses the modelling of the cognitive and evolutionary aspects of engineering design in support of two broad goals: the better understanding of product life cycle processes, and the development of relevant information infrastructure services. The modelling elements are derived from the Framework of Industrial Semiosis. The semiosis of evolutionary design is explained, and general principles of the evolution of the product concept are formulated

Non-Linear Elasticity of Extracellular Matrices Enables Contractile Cells to Communicate Local Position and Orientation

Most tissue cells grown in sparse cultures on linearly elastic substrates typically display a small, round phenotype on soft substrates and become increasingly spread as the modulus of the substrate increases until their spread area reaches a maximum value. As cell density increases, individual cells retain the same stiffness-dependent differences unless they are very close or in molecular contact. On nonlinear strain-stiffening fibrin gels, the same cell types become maximally spread even when the low strain elastic modulus would predict a round morphology, and cells are influenced by the presence of neighbors hundreds of microns away. Time lapse microscopy reveals that fibroblasts and human mesenchymal stem cells on fibrin deform the substrate by several microns up to five cell lengths away from their plasma membrane through a force limited mechanism. Atomic force microscopy and rheology confirm that these strains locally and globally stiffen the gel, depending on cell density, and this effect leads to long distance cell-cell communication and alignment. Thus cells are acutely responsive to the nonlinear elasticity of their substrates and can manipulate this rheological property to induce patterning