Non-invasive Chromatin Deformation and Measurement of Differential Mechanical Properties in the Nucleus

The nucleus is highly organized to facilitate coordinated gene transcription. Measuring the rheological properties of the nucleus and its sub-compartments will be crucial to understand the principles underlying nuclear organization. Here, we show that strongly localized temperature gradients (approaching 1°C /μm) can lead to substantial intra-nuclear chromatin displacements (>1 μm), while nuclear area and lamina shape remain unaffected. Using particle image velocimetry (PIV), intra-nuclear displacement fields can be calculated and converted into spatio-temporally resolved maps of various strain components. Using this approach, we show that chromatin displacements are highly reversible, indicating that elastic contributions are dominant in maintaining nuclear organization on the time scale of seconds. In genetically inverted nuclei, centrally compacted heterochromatin displays high resistance to deformation, giving a rigid, solid-like appearance. Correlating spatially resolved strain maps with fluorescent reporters in conventional interphase nuclei reveals that various nuclear compartments possess distinct mechanical identities. Surprisingly, both densely and loosely packed chromatin showed high resistance to deformation, compared to medium dense chromatin. Equally, nucleoli display particularly high rigidity and strong local anchoring to heterochromatin. Our results establish how localized temperature gradients can be used to drive nuclear compartments out of mechanical equilibrium to obtain spatial maps of their material responses.

Strain Response in the Facet Joint Capsule During Physiological Joint Rotation and Translation Following a Simulated Impact Exposure: an in Vitro Porcine Model

Low back pain (LBP) is frequently reported following rear impact collisions. Knowledge of how the facet joint capsule (FJC) mechanically behaves before and after rear impact collisions may help explain LBP development despite negative radiographic evidence of gross tissue failure. This study quantified the Green strain tensor in the facet joint capsule during rotation and translation range-of-motion tests completed before and following an in vitro simulation of a rear impact collision. Eight FSUs (4 C3-C4, 4 C5-C6) were tested. Following a preload test, FSUs were flexed and extended at 0.5 degrees/second until an ±8 Nm moment was achieved. Anterior and posterior joint translation was then applied at 0.2 mm/s until a target ±400 N shear load was imposed. Markers were drawn on the facet capsule surface and their coordinates were tracked during pre- and post-impact range-of-motion tests. Strain was defined as the change in point configuration relative to the determined neutral joint posture. There were no significant differences (p > 0.05) observed in all calculated FJC strain components in rotation and translation before and after the simulated impact. Our results suggest that LBP development resulting from the initiation of strain-induced mechanoreceptors and nociceptors with the facet joint capsule is unlikely following a severe rear impact collision within the boundaries of physiological joint motion.

Synchrotron 4D X-Ray Imaging Reveals Strain Localization at the Onset of System-Size Failure in Porous Reservoir Rocks

Understanding the mechanisms of strain localization leading to brittle failure in reservoir rocks can shed light on geomechanical processes such as porosity and permeability evolution during rock deformation, induced seismicity, fracturing, and subsidence in geological reservoirs. We perform triaxial compression tests on three types of porous reservoir rocks to reveal the local deformation mechanisms that control system-size failure. We deformed cylindrical samples of Adamswiller sandstone (23% porosity), Bentheim sandstone (23% porosity), and Anstrude limestone (20% porosity), using an X-ray transparent triaxial deformation apparatus. This apparatus enables the acquisition of three-dimensional synchrotron X-ray images, under in situ stress conditions. Analysis of the tomograms provide 3D distributions of the microfractures and dilatant pores from which we calculated the evolving macroporosity. Digital volume correlation analysis reveals the dominant strain localization mechanisms by providing the incremental strain components of pairs of tomograms. In the three rock types, damage localized as a single shear band or by the formation of conjugate bands at failure. The porosity evolution closely matches the evolution of the incremental strain components of dilation, contraction, and shear. With increasing confinement, the dominant strain in the sandstones shifts from dilative strain (Bentheim sandstone) to contractive strain (Adamswiller sandstone). Our study also links the formation of compactive shear bands with porosity variations in Anstrude limestone, which is characterized by a complex pore geometry. Scanning electron microscopy images indicate that the microscale mechanisms guiding strain localization are pore collapse and grain crushing in sandstones, and pore collapse, pore-emanated fractures and cataclasis in limestones. Our dynamic X-ray microtomography data brings unique insights on the correlation between the evolutions of rock microstructure, porosity evolution, and macroscopic strain during the approach to brittle failure in reservoir rocks.

In-silico study of accuracy and precision of left-ventricular strain quantification from 3D tagged MRI

Cardiac Magnetic Resonance Imaging (MRI) allows quantifying myocardial tissue deformation and strain based on the tagging principle. In this work, we investigate accuracy and precision of strain quantification from synthetic 3D tagged MRI using equilibrated warping. To this end, synthetic biomechanical left-ventricular tagged MRI data with varying tag distance, spatial resolution and signal-to-noise ratio (SNR) were generated and processed to quantify errors in radial, circumferential and longitudinal strains relative to ground truth. Results reveal that radial strain is more sensitive to image resolution and noise than the other strain components. The study also shows robustness of quantifying circumferential and longitudinal strain in the presence of geometrical inconsistencies of 3D tagged data. In conclusion, our study points to the need for higher-resolution 3D tagged MRI than currently available in practice in order to achieve sufficient accuracy of radial strain quantification.

Incremental value of left atrial booster and reservoir strain in predicting atrial fibrillation in patients with hypertrophic cardiomyopathy: a cardiovascular magnetic resonance study

Background Left atrial (LA) size and function are known predictors of new onset atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients. Components of LA deformation including reservoir, conduit, and booster function provide additional information on atrial mechanics. Whether or not LA deformation can augment our ability to predict the risk of new onset AF in HCM patients beyond standard measurements is unknown. Methods We assessed LA size, function, and deformation on cardiovascular magnetic resonance (CMR) in 238 genotyped HCM patients and compared this with twenty age, sex, blood pressure and body mass index matched control subjects. We further evaluated the determinants of new onset AF in HCM patients. Results Compared to control subjects, HCM patients had higher LA antero-posterior diameter, lower LA ejection fraction and lower LA reservoir (19.9 [17.1, 22.2], 21.6 [19.9, 22.9], P = 0.047) and conduit strain (10.6 ± 4.4, 13.7 ± 3.3, P = 0.002). LA booster strain did not differ between healthy controls and HCM patients, but HCM patients who developed new onset AF (n = 33) had lower booster strain (7.6 ± 3.3, 9.5 ± 3.0, P = 0.001) than those that did not (n = 205). In separate multivariate models, age, LA ejection fraction, and LA booster and reservoir strain were each independent determinants of AF. Age ≥ 55 years was the strongest determinant (HR 6.62, 95% CI 2.79–15.70), followed by LA booster strain ≤ 8% (HR 3.69, 95% CI 1.81–7.52) and LA reservoir strain ≤ 18% (HR 2.56, 95% CI 1.24–5.27). Conventional markers of HCM phenotypic severity, age and sudden death risk factors were associated with LA strain components. Conclusions LA strain components are impaired in HCM and, together with age, independently predicted the risk of new onset AF. Increasing age and phenotypic severity were associated with LA strain abnormalities. Our findings suggest that the routine assessment of LA strain components and consideration of age could augment LA size in predicting risk of AF, and potentially guide prophylactic anticoagulation use in HCM.

Biomechanical Properties of Bone and Mucosa for Design and Application of Dental Implants

Dental implants’ success comprises their proper stability and adherence to different oral tissues (integration). The implant is exposed to different mechanical stresses from swallowing, mastication and parafunctions for a normal tooth, leading to the simultaneous mechanical movement and deformation of the whole structure. The knowledge of the mechanical properties of the bone and gingival tissues in normal and pathological conditions is very important for the successful conception of dental implants and for clinical practice to access and prevent potential failures and complications originating from incorrect mechanical factors’ combinations. The challenge is that many reported biomechanical properties of these tissues are substantially scattered. This study carries out a critical analysis of known data on mechanical properties of bone and oral soft tissues, suggests more convenient computation methods incorporating invariant parameters and non-linearity with tissues anisotropy, and applies a consistent use of these properties for in silico design and the application of dental implants. Results show the advantages of this approach in analysis and visualization of stress and strain components with potential translation to dental implantology.

Investigation of Deformation Inhomogeneity and Low-Cycle Fatigue of a Polycrystalline Material

Considering the relationship between inhomogeneous plastic deformation and fatigue damage, deformation inhomogeneity evolution and fatigue failure of superalloy GH4169 under temperature 500 °C and macro tension compression cyclic loading are studied, by using crystal plasticity calculation associated with polycrystalline representative Voronoi volume element (RVE). Different statistical standard deviation and differential entropy of meso strain are used to measure the inhomogeneity of deformation, and the relationship between the inhomogeneity and strain cycle is explored by cyclic numerical simulation. It is found from the research that the standard deviations of each component of the strain tensor at the cyclic peak increase monotonically with the cyclic loading, and they are similar to each other. The differential entropy of each component of the strain tensor also increases with the number of cycles, and the law is similar. On this basis, the critical values determined by statistical standard deviations of the strain components and the equivalent strain, and that by differential entropy of strain components, are, respectively, used as fatigue criteria, then predict the fatigue–life curves of the material. The predictions are verified with reference to the measured results, and their deviations are proved to be in a reasonable range.

Distributed Fibre Optic Sensor-Based Continuous Strain Measurement along Semicircular Paths Using Strain Transformation Approach

Distributed fibre optic sensors (DFOS) are popular for structural health monitoring applications in large engineering infrastructure because of their ability to provide spatial strain measurements continuously along their lengths. Curved paths, particularly semicircular paths, are quite common for optical fibre placement in large structures in addition to straight paths. Optical fibre sensors embedded in a curved path configuration typically measure a component of strain, which often cannot be validated using traditional approaches. Thus, for most applications, strain measured along curved paths is ignored as there is no proper validation tool to ensure the accuracy of the measured strains. To overcome this, an analytical strain transformation equation has been developed and is presented here. This equation transforms the horizontal and vertical strain components obtained along a curved semicircular path into a strain component, which acts tangentially as it travels along the curved fibre path. This approach is validated numerically and experimentally for a DFOS installed on a steel specimen with straight and curved paths. Under tensile and flexural loading scenarios, the horizontal and vertical strain components were obtained numerically using finite element analysis and experimentally using strain rosettes and then, substituted into the proposed strain transformation equation for deriving the transformed strain values. Subsequently, the derived strain values obtained from the proposed transformation equation were validated by comparing them with the experimentally measured DFOS strains in the curved region. Additionally, this study has also shown that a localised damage to the DFOS coating will not impact the functionality of the sensor at the remaining locations along its length. In summary, this paper presents a valid strain transformation equation, which can be used for transforming the numerical simulation results into the DFOS measurements along a semicircular path. This would allow for a larger scope of spatial strains measurements, which would otherwise be ignored in practice.