Regulation of scleral cell contraction by transforming growth factor-β and stress competing roles in myopic growth

Reduced extracellular matrix accumulation in the sclera of myopic eyes leads to increased ocular extensibility and is related to reduced levels of scleral transforming growth factor-β (TGF-β). The current study investigated the impact of this extracellular environment on scleral cell phenotype and cellular biomechanical characteristics. Scleral cell phenotype was investigated in vivo in a mammalian model of myopia using the myofibroblast marker, α-smooth muscle actin (α-SMA). In eyes developing myopia α-SMA levels were increased, suggesting increased numbers of contractile myofibroblasts, and decreased in eyes recovering from myopia. To understand the factors regulating this change in scleral phenotype, the competing roles of TGF-β and mechanical stress were investigated in scleral cells cultured in three-dimensional collagen gels. All three mammalian isoforms of TGF-β altered scleral cell phenotype to produce highly contractile, α-SMA-expressing myofibroblasts (TGF-β3 > TGF-β2 > TGF-β1). Exposure of cells to the reduced levels of TGF-β found in the sclera in myopia produced decreased cell-mediated contraction and reduced α-SMA expression. These findings are contrary to the in vivo gene expression data. However, when cells were exposed to both the increased stress and the reduced levels of TGF-β found in myopia, increased α-SMA expression was observed, replicating in vivo findings. These results show that although reduced scleral TGF-β is a major contributor to the extracellular matrix remodeling in the myopic eye, it is the resulting increase in scleral stress that dominates the competing TGF-β effect, inducing increased α-SMA expression and, hence, producing a larger population of contractile cells in the myopic eye.

Effect of transformation volume contraction on the toughness of superelastic shape memory alloys

Shape memory alloys (SMAs) exhibit two very important properties: shape memory phenomenon and superelastic deformation due to intrinsic thermoelastic martensitic transformation. To fully exploit the potential of SMAs in developing functional structures or smart structures in mechanical and biomechanical engineering, it is important to understand and quantify the failure mechanisms of SMAs. This paper presents a theoretical study of the effect of phase-transformation-induced volume contraction on the fracture properties of superelastic SMAs. A simple model is employed to account for the forward and reverse phase transformation with pure volume change, which is then applied to numerically study the transformation field near the tip of a tensile crack. The results reveal that during steady-state crack propagation, the transformation zone extends ahead of the crack tip due to forward transformation while partial reverse transformation occurs in the wake. Furthermore, as a result of the volume contraction associated with the austenite-to-martensite transformation, the induced stress-intensity factor is positive. This is in stark contrast with the negative stress-intensity factor achieved in zirconia ceramics, which undergoes volume expansion during phase transformation. The reverse transformation has been found to have a negligible effect on the induced stress-intensity factor. An important implication of the present results is that the phase transformation with volume contraction in SMAs tends to reduce their fracture resistance and increase the brittleness.

Twinning and the ductility of magnesium alloys Part II. “Contraction” twins

Magnesium and its alloys do not in general undergo the same extended range of plasticity as their competitor structural metals. The present work presents part II of a study that examines some of the roles deformation twinning might play in the phenomenon. A series of tensile and compression tests results are reported for common wrought alloys: AZ31, ZK60 and ZM20. These data are combined with EBSD analysis and simple flow stress models to argue the following: (i) that “contraction” double twinning (which enables contraction along the c axis) can decrease the uniform elongation, and (ii) that compression double twinning can also account for shear failure at low strains. The last of these is described as a combined consequence of strain softening of the continuum and the local generation of twin sized voids.

Effect of resistance exercise contraction mode and protein supplementation on members of the STARS signalling pathway

The striated muscle activator of Rho signalling (STARS) pathway is suggested to provide a link between external stress responses and transcriptional regulation in muscle. However, the sensitivity of STARS signalling to different mechanical stresses has not been investigated. In a comparative study, we examined the regulation of the STARS signalling pathway in response to unilateral resistance exercise performed as either eccentric (ECC) or concentric (CONC) contractions as well as prolonged training; with and without whey protein supplementation. Skeletal muscle STARS, myocardian-related transcription factor-A (MRTF-A) and serum response factor (SRF) mRNA and protein, as well as muscle cross-sectional area and maximal voluntary contraction, were measured. A single-bout of exercise produced increases in STARS and SRF mRNA and decreases in MRTF-A mRNA with both ECC and CONC exercise, but with an enhanced response occurring following ECC exercise. A 31% increase in STARS protein was observed exclusively after CONC exercise (P < 0.001), while pSRF protein levels increased similarly by 48% with both CONC and ECC exercise (P < 0.001). Prolonged ECC and CONC training equally stimulated muscle hypertrophy and produced increases in MRTF-A protein of 125% and 99%, respectively (P < 0.001). No changes occurred for total SRF protein. There was no effect of whey protein supplementation. These results show that resistance exercise provides an acute stimulation of the STARS pathway that is contraction mode dependent. The responses to acute exercise were more pronounced than responses to accumulated training, suggesting that STARS signalling is primarily involved in the initial phase of exercise-induced muscle adaptations.