Mitochondria are double-membrane organelles with varying shapes influenced by metabolic conditions, developmental stage, and environmental stimuli1–4. Their dynamic morphology is realized through regulated and balanced fusion and fission processes5, 6. Fusion is crucial for the health and physiological functions of mitochondria, including complementation of damaged mitochondrial DNAs and maintenance of membrane potential6–8. Mitofusins (Mfns) are dynamin-related GTPases essential for mitochondrial fusion9, 10. They are embedded in the mitochondrial outer membrane and thought to fuse adjacent mitochondria via concerted oligomerization and GTP hydrolysis11–13. However, the molecular mechanisms behind this process remains elusive. Here we present crystal structures of engineered human Mfn1 containing the GTPase domain and a helical domain in different stages of GTP hydrolysis. The helical domain is composed of elements from widely dispersed sequence regions of Mfn1 and resembles the Neck of the bacterial dynamin-like protein. The structures reveal unique features of its catalytic machinery and explain how GTP binding induces conformational changes to promote G domain dimerization in the transition state. Disruption of G domain dimerization abolishes the fusogenic activity of Mfn1. Moreover, a conserved aspartate trigger was found in Mfn1 to affect mitochondrial elongation, likely through a GTP-loading-dependent domain rearrangement. Based on these results, we propose a mechanistic model for Mfn1-mediated mitochondrial tethering. Our study provides important insights in the molecular basis of mitochondrial fusion and mitofusin-related human neuromuscular disorders14.
The regularly shaped parallel pore gas armed (GASAR) stainless steel porous material with a homogeneous size distribution of unusually micrometer scaled pores (2 mm in average) was successfully prepared using selective laser melting process, by adding 0?10 wt-% gas generating materials in the form of H 3 BO 3 and KBF 4 . The adjustment of pore morphology, pore direction, and porosity was realised by changing material combinations (such as the content of additive materials) and processing conditions (such as the scan speed of laser beam).
Recent advances in direct metal laser sintering (DMLS) have improved this technique considerably; however, it still remains limited in terms of material versatility and controllability of laser processing. In the present work, a multicomponent Cu based metal powder, which consisted of a mixture of Cu, Cu-10Sn and Cu-8 . 4P powder, was developed for DMLS. Sound sintering activities and high densification response were obtained by optimising the powder characteristics and manipulating the processing conditions. Investigations on the microstructural evolution in the laser sintered powder show that liquid phase sintering with partial or complete melting of the binder (Cu-10Sn), but non-melting of the cores of structural metal (Cu) acts as the feasible mechanism of particle bonding. The additive phosphorus acts as a fluxing agent to protect the Cu particles from oxidation and shows a concentration along grain boundaries owing to the low solubility of P in Cu and the short thermal cycle of laser sintering. A directionally solidified microstructure consisting of significantly refined grains is formed, which may be ascribed to laser induced non-equilibrium effects such as high temperature gradient and rapid solidification.
In this study, laser metal deposition (LMD) additive manufacturing was used to deposit the pure Inconel 625 alloy and the TiC/Inconel 625 composites with different starting sizes of TiC particles, respectively. The influence of the additive TiC particle and its original size on the constitutional phases, microstructural features, and mechanical properties of the LMD-processed parts was studied. The incorporation of TiC particles significantly changed the prominent texture of Ni–Cr matrix phase from (200) to (100). The bottom and side parts of each deposited track showed mostly the columnar dendrites, while the cellular dendrites were prevailing in the microstructure of the central zone of the deposited track. As the nano-TiC particles were added, more columnar dendrites were observed in the solidified molten pool. The incorporation of nano-TiC particles induced the formation of the significantly refined columnar dendrites with the secondary dendrite arms developed considerably well. With the micro-TiC particles added, the columnar dendrites were relatively coarsened and highly degenerated, with the secondary dendrite growth being entirely suppressed. The cellular dendrites were obviously refined by the additive TiC particles. When the nano-TiC particles were added to reinforce the Inconel 625, the significantly improved microhardness, tensile property, and wear property were obtained without sacrificing the ductility of the composites.
Direct laser sintering of a multicomponent Cu based metal powder was successfully processed through the mechanism of liquid phase sintering with partial melting of the powder. The effects of processing parameters such as laser power, scan speed, scan line spacing and layer thickness on the densification and microstructural evolution of the laser sintered powder were investigated. It was found that with increasing laser power or decreasing scan speed, the density of the sintered parts increased and the microstructures became denser. However, the combination of higher laser powers (.400 W) and higher scan speeds (>0 . 06 ms 21 ) gave rise to 'balling' effect. A successive transition from discontinuous scan tracks to coherently joined ones occurs with decreasing scan line spacing. Lowering the thickness of the powder layer promises an improvement in bonding coherence between sintered layers. A single factor termed 'energy density by volume' is defined to evaluate the combined effect of various processing parameters on the density of laser sintered powder. With increasing the energy density by volume up to ,0 . 16 kJ mm 23 , the densification rate is relatively high. However, with intensifying the energy density over ,0 . 23 kJ mm 23 , the mechanism of particle bonding may change into full melting/ solidification, leading to a decrease in the sintered density.
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