Anisotropic stiffness and tensional homeostasis induce a natural anisotropy of volumetric growth and remodeling in soft biological tissues

Biomechanics and Modeling in Mechanobiology - Growth in soft biological tissues in general results in anisotropic changes of the tissue geometry. It remains a key challenge in biomechanics to...     

Passive and active reactions of embryonic tissues to the action of dosed mechanical forces

With the help of a suction manometric device, the relation between the deformation of Xenonus laevis embryo at the gastrula and neurula stages and the value of the applied force has been studied. Stiffness modules of embryonic tissues were in the order of several dozens of Pascal and they were inversely proportional during deformation from 40 to 20%. At the gastrula stage, a uniform or an increasing rate of expansion of the embryo body in the suction capillary with the diameter of approximately half that of the embryo was observed for 30 min after the action of the suction forces. The length of the stretched portion of the embryo correlates with the value of its deformation at the first minute. As a result of the expansion, the total body surface area of the deformed embryo increases more than twice compared to intact embryos. After expelling the embryo from the capillary, its surface reduced and the deformation became smoothened within 5 min, which indicates the existence of tensional force in the expanded embryo. These data confirm that, at the embryo gastrula stage, external mechanical forces do not only passively deform the embryo but also initiate the active expansion of the embryo which takes place at zero external force and overcomes the tensional resistance of tissues. The mechanism of active expansion and its link with the processes of normal morphogenesis are discussed.     

The effect of shear forces externally applied to skin surface on underlying tissues

The effects of shear forces externally applied to the skin surface on the underlying tissues have been investigated. An analysis of the internal stresses and strains was conducted using a simplified model incorporating elasticity theory. Skin blood flow was measured using laser Doppler flowmetry while variable shear forces over a range of 0–250g were applied to the skin surface. The theoretical model predicts that the application of surface shear forces alters the internal stress distribution and makes the shear and compressive components of stresses increase ahead of the surface force application point. The force resulting from concomitant application of shear and normal force determines the internal maximum stress and strain. Theoretically, the shear force should have the same effects on the underlying tissues as normal force. The experimental investigations revealed that the skin blood flow decreased roughly linearly with the increase of shear forces. When a shear force equal to the normal force was applied, the flux decreased by 45%, nearly equal to the increasing magnitude (41%) of resultant of normal and shear forces.     

Epr analysis reveals three tissues responding to endotoxin by increased formation of reactive oxygen and nitrogen species

The excessive formation of reactive oxygen and nitrogen species (RONS) in tissue has been implicated in the development of various diseases. In this study we adopted ex vivo low temperature EPR spectroscopy combined with spin trapping technique to measure local RONS levels in frozen tissue samples. CP-H (1-hydroxy-3-carboxy-pyrrolidine), a new nontoxic spin probe, was used to analyze RONS in vivo. In addition, nitrosyl complexes of hemoglobin were determined to trace nitric oxide released into blood. By this technique we found that RONS formation in tissue of control animals increased in the following order: liver < heart < brain < cerebellum < lung < muscle < blood < ileum < kidney < duodenum < jejunum. We also found that endotoxin challenge, which represents the most common model of septic shock, increased the formation of RONS in rat liver, heart, lung, and blood, but decreased RONS formation in jejunum. We did not find changes in RONS levels in other parts of gut, brain, skeletal muscles, and kidney. Scavenging of RONS by CP-H was accompanied by an increase in blood pressure, indicating that LPS-induced vasodilatation may be due to RONS, but not due to nitric oxide. Experiments with tissue homogenates incubated in vitro with CP-H showed that ONOO⁻ and O₂^•−, as well as other not identified RONS, are detectable by CP-H in tissue. In summary, low-temperature EPR combined with CP-H infusion allowed detection of local RONS formation in tissues. Increased formation of RONS in response to endotoxin challenge is organ specific.     

Cellular stiffness response to external deformation: tensional homeostasis in a single fibroblast

Stiffness responses of fibroblasts were measured by scanning probe microscopy, following elongation or compression by deformation of an elastic substrate by 8%. The cellular stiffness, reflecting intracellular tension acting along stress fibers, decreased or increased instantly in response to the elongating or compressing stimuli, respectively. After this rapid change, the fibroblasts gradually recovered to their initial stiffness during the following 2 h, and then stabilized. The cells did not show conspicuous changes in shape after the 8% deformation during the SPM measurements. Fluorescence examination for GFP-actin demonstrated that the structure of the stress fibers was not altered noticeably by this small degree of deformation. Treatment with Y-27632, to inhibit myosin phosphorylation and abrogate cellular contractility, eliminated the change in stiffness after the mechanical elongation. These results indicate that fibroblasts possess a mechanism that regulates intracellular tension along stress fibers to maintain the cellular stiffness in a constant equilibrium state.     

Within-session modulation of timed anticipatory responding: When to start responding

The peak procedure is widely used in the study of interval timing with animals. Multiple timing measures can be derived from peak responding. These measures are typically presented as averages across many trials based on the implicit assumption that peak responding is stable throughout the session. We tested this assumption by examining whether peak responding changed over the course of the session in 45 mice that were trained on a fixed-interval 30-s schedule. All common measures of peak responding, except stop times, changed over the course of the session: start times increased, response rates and spreads decreased, and, although less reliably, peak times also shifted rightward. These results are congruent with a motivational interpretation, whereby increased satiety leads to the observed behavioral signature of within-session modulation of timed anticipatory responding.     

A new in vivo technique for 3-dimensional analysis of the translation of femoral condyles and the menisci responding to antagonistic muscle forces]

The aim of our study was to develop a 3-D MR-based technique for the analysis of meniscal and femoral translations during flexion of the knee, and under the influence of antagonistic muscle forces in healthy subjects. In an open MR system, 5 knees were examined at 30 degrees and 90 degrees flexion using a T1-weighted 3-D gradient echo sequence. A force of 30 Newtons, first in the extending and then in the flexing direction, was applied to the distal lower leg. After three-dimensional reconstruction, the minimal distances between the centre of the tibial plateau and the posterior edge of the menisci and femoral condyles were determined. At 30 degrees flexion, the minimum distance for the meniscus was larger medially than laterally (23.2 +/- 1.8 mm vs. 16.2 +/- 3.3 mm), and this also applied to the condyles (25.1 +/- 1.5 vs. 19.0 +/- 3.0 mm). During flexion to 90 degrees, a posterior translation of 0.5 +/- 0.2 mm was observed for the lateral, and of 3.4 +/- 1.2 mm for the medial, meniscus. The condyles demonstrated a different posterior translation (lateral 2.2 +/- 0.56 mm; medial 1.8 +/- 1.9 mm). No obvious differences were found between extension and flexion muscle activity for the different positions of the knee. In the present study, a new 3-D technique is presented for the analysis of the femoral and meniscal translation at various positions of the knee, and under muscle activity. The results suggest different translation for the menisci and condyles.     

Extensor Tendon Injury Due to Repetitive Wrist Dorsiflexion: Morphological Study of Extensor Retinaculum and Extensor Tendon

Most etiological studies of extensor tendon injury were based on the normal anatomy of extensor tendon and extensor retinaculum of the wrist. Further understanding of the morphological changes of the extensor tendon and extensor retinaculum during wrist dorsiflexion might contribute to improved and more accurate understanding of the etiology. The morphology of the extensor tendon of the mid-finger and the fourth compartment of the wrist extensor retinaculum was studied by sonography, and the anatomy was studied in 15 extremities from 11 young male cadavers. Compared with anatomical images, ultrasonography provides similar morphological observations of the extensor retinaculum of the wrist and extensor tendon. Ultrasonography findings revealed that as the dorsiflexion angle changed, the extensor retinaculum of the wrist formed different shaped trochleas. The trochlea guides the rotation of the extensor tendon at the wrist, but it does not form a sharp corner with the extensor tendon; thus, the extensor tendon is not compressed. As the dorsiflexion angle increased from 0° to 60°, the length of the trochlea gradually decreases. The shortening of the trochlea length will lead to a smaller frictional contact area between the extensor tendon and the extensor retinaculum. Consequently, the friction is centralized. During wrist dorsiflexion, the extensor retinaculum provides a trochlea for the extensor tendon. Extensor tendon injury of repetitive wrist dorsiflexion might be caused by centralized friction at the small contact area.     

Rapid and reversible modifications of extension capacity of cell walls in elongating maize leaf tissues responding to root addition and removal of NaCl

A creep extensiometer technique was used to provide direct evidence that short (20 min) and long-term (3d) exposures of roots to growth inhibitory levels of salinity (100mol m^-3 NaCl) induce reductions in the irreversible extension capacity of cell walls in the leaf elongation zone of intact maize seedlings (Zea mays L.). The long-term inhibition of cell wall extension capacity was reversed within 20 min of salt withdrawal from the root medium. Inhibited elongation of leaf epidermal tissues was also reversed after salt removal. The salt-induced changes in wall extension capacity were detected using in vivo and in vitro assays (shortly after localized freeze/thaw treatment of the basal elongation zone). The rapid reversal of the inhibition of wall extensibility and leaf growth after salt removal from root medium of long-term salinized plants, suggested that neither deficiencies in growth essential mineral nutrients nor toxic effects of NaCl on plasmamembrane viability were directly involved in the inhibition of leaf growth. There was consistent agreement between the scale, direction and timing of salinity-induced changes in leaf elongation growth and wall extension capacity. Rapid metabolically regulated changes in the physical properties of growing cell walls, caused by osmotic (or other) effects, appear to be a factor regulating maize leaf growth responses to root salinization.     

防止肌腱粘连及促进其愈合的研究进展

随着对肌腱愈合研究的不断深入和发展,预防肌腱粘连以及促进其愈合的方法越来越多。通过改进缝合方法、修复腱鞘或采用替代品、置入药物或药物薄膜及早期康复等治疗来有效预防肌腱粘连;通过重建腱鞘、药物、生长因子、基因干预等促进肌腱愈合。本文就近年来防止肌腱粘连及促进其愈合方面的研究予以综述。     

miRNA-mediated macrophage behaviors responding to matrix stiffness and ox-LDL

Atherosclerosis is one of the leading causes of morbidity and mortality, mainly due to the immune response triggered by the recruitment of monocytes/macrophages in the artery wall. Accumulating evidence have shown that matrix stiffness and oxidized low-density lipoproteins (ox-LDL) play important roles in atherosclerosis through modulating cellular behaviors. However, whether there is a synergistic effect for ox-LDL and matrix stiffness on macrophages behavior has not been explored yet. In this study, we developed a model system to investigate the synergistic role of ox-LDL and matrix stiffness on macrophage behaviors, such as migration, inflammatory and apoptosis. We found that there was a matrix stiffness-dependent behavior of monocyte-derived macrophages stimulated with ox-LDL. What's more, macrophages were more sensitive to ox-LDL on the stiff matrices compared to cells cultured on the soft matrices. Through next-generation sequencing, we identified miRNAs in response to matrix stiffness and ox-LDL and predicted pathways that showed the capability of miRNAs in directing macrophages fates. Our study provides a novel understanding of the important synergistic role of ox-LDL and matrix stiffness in modulating macrophages behaviors, especially through miRNAs signaling pathways, which could be potential key regulators in atherosclerosis and immune-targeted therapies.