Enhanced virulence of Salmonella enterica serovar typhimurium after passage through mice.

The interaction between Salmonella enterica and the host immune system is complex. The outcome of an infection is the result of a balance between the in vivo environment where the bacteria survive and grow and the regulation of fitness genes at a level sufficient for the bacteria to retain their characteristic rate of growth in a given host. Using bacteriological counts from tissue homogenates and fluorescence microscopy to determine the spread, localization, and distribution of S. enterica in the tissues, we show that, during a systemic infection, S. enterica adapts to the in vivo environment. The adaptation becomes a measurable phenotype when bacteria that have resided in a donor animal are introduced into a recipient naïve animal. This adaptation does not confer increased resistance to early host killing mechanisms but can be detected as an enhancement in the bacterial net growth rate later in the infection. The enhanced growth rate is lost upon a single passage in vitro, and it is therefore transient and not due to selection of mutants. The adapted bacteria on average reach higher intracellular numbers in individual infected cells and therefore have patterns of organ spread different from those of nonadapted bacteria. These experiments help in developing an understanding of the influence of passage in a host on the fitness and virulence of S. enterica.

A model for nonlinear viscoelastic mechanical responses of collagenous soft tissues

Experimental observations of the time-dependent mechanical responses of collagenous tissues have demonstrated behavior that deviates from standard treatments of linear or quasi-linear viscoelasticity. In particular, time-dependent deformation can be strongly coupled to strain level, and strain-rate independence can be observed under monotonic loading, even for a tissue with dramatic stress relaxation. It was postulated that this nonlinearity is fundamentally associated with gradual recruitment of individual collagen fibrils during applied mechanical loading. Based on previously observed experimental results for the time-dependent response of collagenous soft tissues, a model is developed to describe the mechanical behavior of these tissues under uniaxial loading. Tissue stresses, under applied strain-controlled loading, are assumed to be a sum of elastic and viscoelastic stress contributions. The relative contributions of elastic and viscoelastic stresses is assumed to vary with strain level, leading to strain- and time-dependent mechanical behavior. The model formulation is examined under conditions of monotonic loading at varying constant strain rates and stress-relaxation at different applied strain levels. The model is compared with experimental data for a membranous biological soft tissue, the amniotic sac, and is found to agree well with experimental results. The limiting behavior of the novel model, at large strains relative to the collagen recruitment, is consistent with the quasi-linear viscoelastic approach. © 2006 Materials Research Society.

Poroelastic indentation analysis for hydrated biological tissues

Indentation techniques are employed for the measurement of mechanical properties of a wide range of materials. In particular, techniques focused at small length-scales, such as nanoindentation and AFM indentation, allow for local characterization of material properties in heterogeneous materials including natural tissues and biomimetic materials. Typical elastic analysis for spherical indentation is applicable in the absence of time-dependent deformation, but is inappropriate for materials with time-dependent responses. Recent analyses for the viscoelastic indentation problem, based on elastic-viscoelastic correspondence, have begun to address the issue of time-dependent deformation during an indentation test. The viscoelastic analysis has been shown to fit experimental indentation data well, and has been demonstrated as useful for characterization of viscoelasticity in polymeric materials and in hydrated mineralized tissues. However, a viscoelastic analysis is not necessarily sufficient for multi-phase materials with fluid flow. In the current work, a poroelastic analysis-based on fluid motion through a porous elastic network-is used to examine spherical indentation creep responses of hydrated biological materials. Both analytical and finite element approaches are considered for the poroelastic Hertzian indentation problem. Modeling results are compared with experimental data from nanoindentation of hydrated bone immersed in water and polar solvents (ethanol, methanol, acetone). Baseline (water-immersed) bone responses are characterized using the poroelastic model and numerical results are compared with altered hydration states due to polar solvents. © 2007 Materials Research Society.

Size effects in indentation of hydrated biological tissues

Fluid flow in biological tissues is important in both mechanical and biological contexts. Given the hierarchical nature of tissues, there are varying length scales at which time-dependent mechanical behavior due to fluid flow may be exhibited. Here, spherical nanoindentation and microindentation testings are used for the characterization of length scale effects in the mechanical response of hydrated tissues. Although elastic properties were consistent across length scales, there was a substantial difference between the time-dependent mechanical responses for large and small contact radii in the same tissue specimens. This difference was far more obvious when poroelastic analysis was used instead of viscoelastic analysis. Overall, indentation testing is a fast and robust technique for characterizing the hierarchical structure of biological materials from nanometer to micrometer length scales and is capable of making quantitative material property measurements to do with fluid flow. © 2011 Materials Research Society.