Anti-parallel β-sheet crystallite as the main component of silk fibroin has attracted much attention due to its superior mechanical properties. In this study, we examine the processes of pulling a peptide chain from ...Anti-parallel β-sheet crystallite as the main component of silk fibroin has attracted much attention due to its superior mechanical properties. In this study, we examine the processes of pulling a peptide chain from β-sheet crystallite using steered molecular dynamics simulations to investigate the rupture behavior of the crystallite. We show that the failure of β-sheet crystallite was accompanied by a propagation of instability of hydrogen-bonds （H-bonds） in the crystallite. In addition, we find that there is an optimum size of the crystallite at which the H-bonds can work cooperatively to achieve the highest shear strength. In addition, we find that the stiffness of loading device and the loading rates have significant effects on the rupture behavior of β-sheet crystallite. The stiff loading device facilitates the rebinding of the Hbond network in the stick-slip motion between the chains, while the soft one suppresses it. Moreover, the rupture force of β-sheet crystallites decreases with loading rate. Particularly, when the loading rate decreases to a critical value, the rupture force of the β-sheet crystallite becomes independent of the loading rates. This study provides atomistic details of rupture behaviors of β-sheet crystallite, and, therefore, sheds valuable light on the underlying mechanism of the superior mechanical properties of silk fibroin.展开更多
It remains a significant challenge to fabricate natural polymer(NP)hydrogels with anti-swelling ability and high strengths in the physiological environment.Herein,theβ-sheet-reinforced NP hydrogel is developed by cop...It remains a significant challenge to fabricate natural polymer(NP)hydrogels with anti-swelling ability and high strengths in the physiological environment.Herein,theβ-sheet-reinforced NP hydrogel is developed by copolymerizing methacrylated gelatin(GelMA)and methacrylated silk fibroin(SFMA)in aqueous solution,followed by ethanol treatment(named GelMA-SFMAAL).Theβ-sheets formed by SFMA can act as a stable physical crosslink to enhance the mechanical properties and prolong the degradation of the GelMA network.Importantly,the chemical crosslinking in the GelMA-SFMA hydrogel prevents excessive aggregation of hydrophobicβ-sheets,thereby avoiding the formation of brittle hydrogel.The obtained GelMA-SFMA-AL hydrogels exhibit considerably enhanced mechanical properties(Young's modulus:0.89–3.68 MPa;tensile strength:0.31–0.96 MPa;toughness:0.09–0.63 MJ/m^(3);compressive modulus:0.78–2.20 MPa;compressive strength:2.65–5.93 MPa)compared with GelMA-SFMA hydrogels(Young's modulus:0.04–0.13 MPa;tensile strength:0.04–0.07 MPa;toughness:0.01–0.02 MJ/m^(3);compressive modulus:0.03–0.09 MPa;compressive strength:0.30–0.64 MPa).A bilayer osteochondral scaffold is constructed via digital light processing(DLP)three-dimensiaonl(3D)printing technology,comprising GelMA-SFMA@diclofenac sodium(DS)-AL as the top layer and GelMA-SFMA@bioactive glass(BG)-AL as the bottom layer.The bilayer hydrogel scaffold is demonstrated to support cell attachment and spreading,and facilitate osteogenic differentiation of rat bone marrow stem cells in vitro.In vivo implantation experiment suggests this bilayer scaffold is promising to be used for osteochondral tissue regeneration.展开更多
Methyl-CpG(mCpG)binding domain(MBD)proteins especially bind with methylated DNA,and are involved in many important biological processes;however,the binding mechanism between insect MBD2/3 and mCpG remains unclear.In t...Methyl-CpG(mCpG)binding domain(MBD)proteins especially bind with methylated DNA,and are involved in many important biological processes;however,the binding mechanism between insect MBD2/3 and mCpG remains unclear.In this study,we identified 2 isoforms of the MBD2/3 gene in Bombyx mori,MBD2/3-S and MBD2/3-L.Binding analysis of MBD2/3-L,MBD2/3-S,and 7 mutant MBD2/3-L proteins deficient inβ1−β6 orα1 in the MBD showed thatβ2−β3-turns in theβ-sheet of the MBD are necessary for the formation of the MBD2/3–mCpG complex;furthermore,other secondary structures,namely,β4−β6 and anα-helix,play a role in stabilizing theβ-sheet structure to ensure that the MBD is able to bind mCpG.In addition,sequence alignment and binding analyses of different insect MBD2/3s indicated that insect MBD2/3s have an intact and conserved MBD that binds to the mCpG of target genes.Furthermore,MBD2/3 RNA interference results showed that MBD2/3-L plays a role in regulating B.mori embryonic development,similar to that of DNA methylation;however,MBD2/3-S withoutβ4−β6 andα-helix does not alter embryonic development.These results suggest that MBD2/3-L recognizes and binds to mCpG through the intactβ-sheet structure in its MBD,thus ensuring silkworm embryonic development.展开更多
In this paper,B3LYP and MP2 methods are used to investigate the binding energy of seventeen antiparallel and parallel β-sheet models. The results indicate that the binding energy obtained from B3LYP calculations is w...In this paper,B3LYP and MP2 methods are used to investigate the binding energy of seventeen antiparallel and parallel β-sheet models. The results indicate that the binding energy obtained from B3LYP calculations is weaker than that obtained from MP2 calculations but the relative binding energy yielded by B3LYP is almost the same as that by MP2. For the antiparallel β-sheets in which two N―H···O═C hydrogen bonds can form either a large hydrogen-bonded ring or a small hydrogen-bonded ring,the binding energy increases obviously when one large ring unit is added,whereas it only changes slightly when one small ring unit is added because of the secondary electrostatic repulsive interaction existing in the small ring unit which is estimated to be about 20 kJ/mol. For the parallel β-sheet models,the binding energy increases almost exactly linearly with the increase of the chain length.展开更多
基金supported by the National Science Foundation of China (Grants 11025208, 11372042, 11221202, and 11202026)the support from CSIRO-Intelligent Processing TCP+1 种基金CAFHS’ Capability Development FundCSIRO-Advanced Materials TCP
文摘Anti-parallel β-sheet crystallite as the main component of silk fibroin has attracted much attention due to its superior mechanical properties. In this study, we examine the processes of pulling a peptide chain from β-sheet crystallite using steered molecular dynamics simulations to investigate the rupture behavior of the crystallite. We show that the failure of β-sheet crystallite was accompanied by a propagation of instability of hydrogen-bonds （H-bonds） in the crystallite. In addition, we find that there is an optimum size of the crystallite at which the H-bonds can work cooperatively to achieve the highest shear strength. In addition, we find that the stiffness of loading device and the loading rates have significant effects on the rupture behavior of β-sheet crystallite. The stiff loading device facilitates the rebinding of the Hbond network in the stick-slip motion between the chains, while the soft one suppresses it. Moreover, the rupture force of β-sheet crystallites decreases with loading rate. Particularly, when the loading rate decreases to a critical value, the rupture force of the β-sheet crystallite becomes independent of the loading rates. This study provides atomistic details of rupture behaviors of β-sheet crystallite, and, therefore, sheds valuable light on the underlying mechanism of the superior mechanical properties of silk fibroin.
基金supported by the National Key Research and Development Program of China(Grant No.2018YFA0703100)。
文摘It remains a significant challenge to fabricate natural polymer(NP)hydrogels with anti-swelling ability and high strengths in the physiological environment.Herein,theβ-sheet-reinforced NP hydrogel is developed by copolymerizing methacrylated gelatin(GelMA)and methacrylated silk fibroin(SFMA)in aqueous solution,followed by ethanol treatment(named GelMA-SFMAAL).Theβ-sheets formed by SFMA can act as a stable physical crosslink to enhance the mechanical properties and prolong the degradation of the GelMA network.Importantly,the chemical crosslinking in the GelMA-SFMA hydrogel prevents excessive aggregation of hydrophobicβ-sheets,thereby avoiding the formation of brittle hydrogel.The obtained GelMA-SFMA-AL hydrogels exhibit considerably enhanced mechanical properties(Young's modulus:0.89–3.68 MPa;tensile strength:0.31–0.96 MPa;toughness:0.09–0.63 MJ/m^(3);compressive modulus:0.78–2.20 MPa;compressive strength:2.65–5.93 MPa)compared with GelMA-SFMA hydrogels(Young's modulus:0.04–0.13 MPa;tensile strength:0.04–0.07 MPa;toughness:0.01–0.02 MJ/m^(3);compressive modulus:0.03–0.09 MPa;compressive strength:0.30–0.64 MPa).A bilayer osteochondral scaffold is constructed via digital light processing(DLP)three-dimensiaonl(3D)printing technology,comprising GelMA-SFMA@diclofenac sodium(DS)-AL as the top layer and GelMA-SFMA@bioactive glass(BG)-AL as the bottom layer.The bilayer hydrogel scaffold is demonstrated to support cell attachment and spreading,and facilitate osteogenic differentiation of rat bone marrow stem cells in vitro.In vivo implantation experiment suggests this bilayer scaffold is promising to be used for osteochondral tissue regeneration.
基金funded by the National Natural Sci-ence Foundation of China,grant numbers 32100374 and 31872286.
文摘Methyl-CpG(mCpG)binding domain(MBD)proteins especially bind with methylated DNA,and are involved in many important biological processes;however,the binding mechanism between insect MBD2/3 and mCpG remains unclear.In this study,we identified 2 isoforms of the MBD2/3 gene in Bombyx mori,MBD2/3-S and MBD2/3-L.Binding analysis of MBD2/3-L,MBD2/3-S,and 7 mutant MBD2/3-L proteins deficient inβ1−β6 orα1 in the MBD showed thatβ2−β3-turns in theβ-sheet of the MBD are necessary for the formation of the MBD2/3–mCpG complex;furthermore,other secondary structures,namely,β4−β6 and anα-helix,play a role in stabilizing theβ-sheet structure to ensure that the MBD is able to bind mCpG.In addition,sequence alignment and binding analyses of different insect MBD2/3s indicated that insect MBD2/3s have an intact and conserved MBD that binds to the mCpG of target genes.Furthermore,MBD2/3 RNA interference results showed that MBD2/3-L plays a role in regulating B.mori embryonic development,similar to that of DNA methylation;however,MBD2/3-S withoutβ4−β6 andα-helix does not alter embryonic development.These results suggest that MBD2/3-L recognizes and binds to mCpG through the intactβ-sheet structure in its MBD,thus ensuring silkworm embryonic development.
基金Supported by the National Natural Science Foundation of China (Grant Nos. 20573049 & 20633050)the Research Fund of the Department of Education of Liaoning Province (Grant Nos. 2007T091 & 20060469)
文摘In this paper,B3LYP and MP2 methods are used to investigate the binding energy of seventeen antiparallel and parallel β-sheet models. The results indicate that the binding energy obtained from B3LYP calculations is weaker than that obtained from MP2 calculations but the relative binding energy yielded by B3LYP is almost the same as that by MP2. For the antiparallel β-sheets in which two N―H···O═C hydrogen bonds can form either a large hydrogen-bonded ring or a small hydrogen-bonded ring,the binding energy increases obviously when one large ring unit is added,whereas it only changes slightly when one small ring unit is added because of the secondary electrostatic repulsive interaction existing in the small ring unit which is estimated to be about 20 kJ/mol. For the parallel β-sheet models,the binding energy increases almost exactly linearly with the increase of the chain length.
