Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides ...Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides that are expressed in the colonic epithelia. This study investigated the effect and the signaling mechanism of inducible β-defensin HBD2 by an essential amino acid, isoleucine (Ile) in colonic epithelial cells. Here we examined the expression level of HBD2 on induction of Ile in epithelial cells, and checked this pathway. HBD2 mRNA was induced by co-incubation with IL-1α and Ile in Caco2 cells, but not by Ile alone. An inhibitor of either ERK or Gi, a subunit of G-proteins, reduced the induction of HBD2 mRNA by Ile. The treatment with Ile also increased the intracellular calcium ion concentration, thus suggesting that the GPCR and ERK signaling pathway mediate the effects of Ile. These results indicate that an essential amino acid, Ile, enhances the expression of an inducible β-defensin, namely HBD2, by IL-1α through the activation of GPCRs and ERK signaling pathway. The administration of Ile may therefore represent a possible option to safely treat intestinal inflammation.展开更多
Mechanical stimulations have been shown to regulate cellular mechanical properties. However, the stimulation patterns for effective regulation are as yet unclear. We investigated the effects of application of differin...Mechanical stimulations have been shown to regulate cellular mechanical properties. However, the stimulation patterns for effective regulation are as yet unclear. We investigated the effects of application of differing numbers of mechanical stimulation sets, each set consisting of 8% extension and compression to cells via deformation of cell culture elastic chamber, on cellular elasticity. Elasticity increased with only a single step-like stretch and with a single step-like stretch after 1 set of mechanical stimulation, whereas elasticity did not change with a single step-like stretch after 10 sets of mechanical stimulation. These results indicate that the increase in cellular elasticity with the single step-like stretch depends on the number of applied mechanical stimulations. Immunofluorescence staining showed that phosphorylation and dephosphorylation of myosin regulatory light chain (MRLC), which regulates intracellular contractile force and cellular elasticity, accompanied cellular elasticity changes. These findings suggest that cellular elasticity changes under cyclic and step-like stretches are mediated by MRLC.展开更多
Synthetic hydrogels can be used as scaffolds that not only favor endothelial cells （ECs） proliferation but also manipulate the behaviors and functions of the ECs. In this review paper, the effect of chemical structu...Synthetic hydrogels can be used as scaffolds that not only favor endothelial cells （ECs） proliferation but also manipulate the behaviors and functions of the ECs. In this review paper, the effect of chemical structure, Young＇s modulus （E） and zeta potential （ζ） of synthetic hydrogel scaffolds on static cell behaviors, including cell morphology, proliferation, cytoskeleton structure and focal adhesion, and on dynamic cell behaviors, including migration velocity and morphology oscillation, as well as on EC function such as anti-platelet adhesion, are reported. It was found that negatively charged hydrogels, poly（2-acrylamido-2-methylpropanesulfonic sodium） （PNaAMPS） and poly（sodium p-styrene sulphonate） （PNaSS）, can directly promote cell proliferation, with no need of surface modifcation by any cell-adhesive proteins or peptides at the environment of serum-containing medium. In addition, the Young＇s modulus （E） and zeta potential （ζ） of hydrogel scaffolds are quantitatively tuned by copolymer hydrogels, poly（NaAMPS-co-DMAAm） and poly（NaSS-co-DMAAm）, in which the two kinds of negatively charged monomers NaAMPS and NaSS are copolymerized with neutral monomer, N,N-dimethylacrylamide （DMAAm）. It was found that the critical zeta potential of hydrogels manipulating EC morphology, proliferation, and motility is ζcritical= -20.83 mV and ζcritical = -14.0 mV for poly（NaAMPS-co-DMAAm） and poly（NaSS-co-DMAAm）, respectively. The above mentioned EC behaviors well correlate with the adsorption of fibronectin, a kind of cell-adhesive protein, on the hydrogel surfaces. Furthermore, adhered platelets on the EC monolayers cultured on the hydrogel scaffolds obviously decreases with an increase of the Young＇s modulus （E） of the hydrogels, especially when E 〉 60 kPa. Glycocalyx assay and gene expression of ECs demonstrate that the anti-platelet adhesion well correlates with the EC-specific glycocalyx. The above investigation suggests that understanding the relationship between physic-chemical properties of synthetic hydrogels and cell responses is essential to design optimal soft and wet scaffolds for tissue engineering. Keywords： Synthetic hydrogel; Scaffold; Endothelial cell; Cell behavior展开更多
Unintentional flaws in materials dramatically reduce their strength and lifespan once they exceed a critical size.Compared to brittle materials such as glass and ceramics,viscoelastic hydrogels,as soft materials,exhib...Unintentional flaws in materials dramatically reduce their strength and lifespan once they exceed a critical size.Compared to brittle materials such as glass and ceramics,viscoelastic hydrogels,as soft materials,exhibit a much greater length of flaw sensitivity length.Understanding the molecular mechanisms that govern flaw sensitivity in viscoelastic materials is crucial for optimizing their applications and designing tough materials.Herein,we use viscoelastic polyampholyte hydrogels as a model system to investigate how the hierarchical structure,including the transient network,primary network,and bicontinuous phase-separated structure,affects the flaw sensitivity length(c_(c)).Our findings reveal that c_(c)is strongly influenced by the primary network but only weakly dependent on the transient network.Furthermore,we estimate the prefactor(1/k)in the relationship between cc and the fractocohesive length(Γ/W^(*)),given by c_(c)=(1/k)Γ/W^(*),which is derived from elastic fracture mechanics,for both viscoelastic and relatively elastic soft materials.Additionally,we identify a universal correlation between cc and the crack blunting indicator-the ratio of fracture stress to Young’s modulus(σ_(f)/E)-which is applicable to both tough elastic and viscoelastic materials.This study offers insights into the mechanisms governing flaw sensitivity in viscoelastic materials.展开更多
Poly(2,2'-disulfonyl-4,4'-benzidine terephthalamide) (PBDT), a kind of liquid-crystalline (LC) molecule, has high molecular weight, negative charge and a semi-rigid structure. The aqueous solution of PBDT show...Poly(2,2'-disulfonyl-4,4'-benzidine terephthalamide) (PBDT), a kind of liquid-crystalline (LC) molecule, has high molecular weight, negative charge and a semi-rigid structure. The aqueous solution of PBDT shows nematic liquid crystalline state above a critical PBDT concentration, CLC*, of 2 wt%-3wt%. Different from the flexible polyelectrolyte, PBDT shows a variety of self-assembling structures in aqueous solution with and without salt due to the semi-rigid nature and highly charged property. In addition, the hydrogels with ordered structure are developed by polymerizing a cationic monomer N-[3-(N,N-dimethylamino) propyl] acrylamide methyl chloride quarternary (DMAPAA-Q) in the presence of a small amount of PBDT below the CLC*. During the polymerization of cationic monomer, the polycations form a complex with semi-rigid PBDT through electrostatic interaction; these complexes self-assemble into ordered structures that are frozen in the hydrogel. Several different structures, including the anisotropic, dual network-like structure, and cylindrically symmetric structure, with various length scales from micrometer to millimeter, are observed. The hydrogels with ordered liquid crystalline assemblies and particular optical properties should promise applications in many fields, such as in bionics, tissue engineering, and mechano-optical sensors.展开更多
Copolymer hydrogels formed from cationic and aromatic monomers with identical monomer compositions but different average sequences were synthesized by free-radical copolymerization in various solvents.We found that hy...Copolymer hydrogels formed from cationic and aromatic monomers with identical monomer compositions but different average sequences were synthesized by free-radical copolymerization in various solvents.We found that hydrogels with one-componentrich segments are mechanically stronger than those with adjacent-rich monomer sequences in water,while hydrogels with a rich cation-πadjacent sequence showed excellent mechanical strength and underwater adhesion in saltwater(0.7 M Na Cl).The molecular mechanisms for these behaviors are discussed in terms of polymer structures.This work reveals the importance of monomeric sequences in determining hydrogel properties and provides a facile approach to develop hydrogels with different properties but the same monomer composition.展开更多
Biological soft tissues and hydrogels belong to the same category of soft and wet matter.Both of them are composed of polymer network and a certain amount of water,and permeable to small molecules.Biological tissues p...Biological soft tissues and hydrogels belong to the same category of soft and wet matter.Both of them are composed of polymer network and a certain amount of water,and permeable to small molecules.Biological tissues possess elaborated structures and exhibit outstanding functionalities.On the other hand,hydrogels are usually amorphous with poor functionality.In recent years,various hydrogels with robust functionalities have been developed by introducing aggregated structures into the gel networks,widely extend their applications in diverse fields,such as soft actuators,biological sensors,and structural biomaterials.Four strategies are usually used to fabricate aggregated structure into hydrogels,including molecular self-assembling,microphase separation,crystallization,and inorganic additives.Different aggregated structures entail the gel very different functionalities.A simple aggregated structure is able to bring multiple functionalities and a combination of mechanical performances of the hydrogels.In this review,we describe the strategies used to construct aggerated structure in hydrogels and discuss about the close relation between the aggregated structure and functionality.We also highlight the role of nonequilibrium aggregated structure in fabricating hydrogels with dynamic memorizing-forgetting behavior and point out the remaining challenges.展开更多
文摘Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides that are expressed in the colonic epithelia. This study investigated the effect and the signaling mechanism of inducible β-defensin HBD2 by an essential amino acid, isoleucine (Ile) in colonic epithelial cells. Here we examined the expression level of HBD2 on induction of Ile in epithelial cells, and checked this pathway. HBD2 mRNA was induced by co-incubation with IL-1α and Ile in Caco2 cells, but not by Ile alone. An inhibitor of either ERK or Gi, a subunit of G-proteins, reduced the induction of HBD2 mRNA by Ile. The treatment with Ile also increased the intracellular calcium ion concentration, thus suggesting that the GPCR and ERK signaling pathway mediate the effects of Ile. These results indicate that an essential amino acid, Ile, enhances the expression of an inducible β-defensin, namely HBD2, by IL-1α through the activation of GPCRs and ERK signaling pathway. The administration of Ile may therefore represent a possible option to safely treat intestinal inflammation.
文摘Mechanical stimulations have been shown to regulate cellular mechanical properties. However, the stimulation patterns for effective regulation are as yet unclear. We investigated the effects of application of differing numbers of mechanical stimulation sets, each set consisting of 8% extension and compression to cells via deformation of cell culture elastic chamber, on cellular elasticity. Elasticity increased with only a single step-like stretch and with a single step-like stretch after 1 set of mechanical stimulation, whereas elasticity did not change with a single step-like stretch after 10 sets of mechanical stimulation. These results indicate that the increase in cellular elasticity with the single step-like stretch depends on the number of applied mechanical stimulations. Immunofluorescence staining showed that phosphorylation and dephosphorylation of myosin regulatory light chain (MRLC), which regulates intracellular contractile force and cellular elasticity, accompanied cellular elasticity changes. These findings suggest that cellular elasticity changes under cyclic and step-like stretches are mediated by MRLC.
文摘Synthetic hydrogels can be used as scaffolds that not only favor endothelial cells （ECs） proliferation but also manipulate the behaviors and functions of the ECs. In this review paper, the effect of chemical structure, Young＇s modulus （E） and zeta potential （ζ） of synthetic hydrogel scaffolds on static cell behaviors, including cell morphology, proliferation, cytoskeleton structure and focal adhesion, and on dynamic cell behaviors, including migration velocity and morphology oscillation, as well as on EC function such as anti-platelet adhesion, are reported. It was found that negatively charged hydrogels, poly（2-acrylamido-2-methylpropanesulfonic sodium） （PNaAMPS） and poly（sodium p-styrene sulphonate） （PNaSS）, can directly promote cell proliferation, with no need of surface modifcation by any cell-adhesive proteins or peptides at the environment of serum-containing medium. In addition, the Young＇s modulus （E） and zeta potential （ζ） of hydrogel scaffolds are quantitatively tuned by copolymer hydrogels, poly（NaAMPS-co-DMAAm） and poly（NaSS-co-DMAAm）, in which the two kinds of negatively charged monomers NaAMPS and NaSS are copolymerized with neutral monomer, N,N-dimethylacrylamide （DMAAm）. It was found that the critical zeta potential of hydrogels manipulating EC morphology, proliferation, and motility is ζcritical= -20.83 mV and ζcritical = -14.0 mV for poly（NaAMPS-co-DMAAm） and poly（NaSS-co-DMAAm）, respectively. The above mentioned EC behaviors well correlate with the adsorption of fibronectin, a kind of cell-adhesive protein, on the hydrogel surfaces. Furthermore, adhered platelets on the EC monolayers cultured on the hydrogel scaffolds obviously decreases with an increase of the Young＇s modulus （E） of the hydrogels, especially when E 〉 60 kPa. Glycocalyx assay and gene expression of ECs demonstrate that the anti-platelet adhesion well correlates with the EC-specific glycocalyx. The above investigation suggests that understanding the relationship between physic-chemical properties of synthetic hydrogels and cell responses is essential to design optimal soft and wet scaffolds for tissue engineering. Keywords： Synthetic hydrogel; Scaffold; Endothelial cell; Cell behavior
基金supported by the Japan Society for the Promotion of Science(JSPS)KAKENHI(JP22K20521 and JP23K13796)the National Natural Science Foundation of China(52273028).
文摘Unintentional flaws in materials dramatically reduce their strength and lifespan once they exceed a critical size.Compared to brittle materials such as glass and ceramics,viscoelastic hydrogels,as soft materials,exhibit a much greater length of flaw sensitivity length.Understanding the molecular mechanisms that govern flaw sensitivity in viscoelastic materials is crucial for optimizing their applications and designing tough materials.Herein,we use viscoelastic polyampholyte hydrogels as a model system to investigate how the hierarchical structure,including the transient network,primary network,and bicontinuous phase-separated structure,affects the flaw sensitivity length(c_(c)).Our findings reveal that c_(c)is strongly influenced by the primary network but only weakly dependent on the transient network.Furthermore,we estimate the prefactor(1/k)in the relationship between cc and the fractocohesive length(Γ/W^(*)),given by c_(c)=(1/k)Γ/W^(*),which is derived from elastic fracture mechanics,for both viscoelastic and relatively elastic soft materials.Additionally,we identify a universal correlation between cc and the crack blunting indicator-the ratio of fracture stress to Young’s modulus(σ_(f)/E)-which is applicable to both tough elastic and viscoelastic materials.This study offers insights into the mechanisms governing flaw sensitivity in viscoelastic materials.
基金supported by a Grant-in-Aid for the Specially Promoted Research (18002002) from the Ministry of Education, Science, Sports and Culture of Japan
文摘Poly(2,2'-disulfonyl-4,4'-benzidine terephthalamide) (PBDT), a kind of liquid-crystalline (LC) molecule, has high molecular weight, negative charge and a semi-rigid structure. The aqueous solution of PBDT shows nematic liquid crystalline state above a critical PBDT concentration, CLC*, of 2 wt%-3wt%. Different from the flexible polyelectrolyte, PBDT shows a variety of self-assembling structures in aqueous solution with and without salt due to the semi-rigid nature and highly charged property. In addition, the hydrogels with ordered structure are developed by polymerizing a cationic monomer N-[3-(N,N-dimethylamino) propyl] acrylamide methyl chloride quarternary (DMAPAA-Q) in the presence of a small amount of PBDT below the CLC*. During the polymerization of cationic monomer, the polycations form a complex with semi-rigid PBDT through electrostatic interaction; these complexes self-assemble into ordered structures that are frozen in the hydrogel. Several different structures, including the anisotropic, dual network-like structure, and cylindrically symmetric structure, with various length scales from micrometer to millimeter, are observed. The hydrogels with ordered liquid crystalline assemblies and particular optical properties should promise applications in many fields, such as in bionics, tissue engineering, and mechano-optical sensors.
基金supported by JSPS KAKENHI Grant(JP17H06144,JP17H06376,JP21K14676)Institute for Chemical Reaction Design and Discovery(WPI-ICRe DD)established by World Premier International Research Initiative(WPI),MEXT,Japan。
文摘Copolymer hydrogels formed from cationic and aromatic monomers with identical monomer compositions but different average sequences were synthesized by free-radical copolymerization in various solvents.We found that hydrogels with one-componentrich segments are mechanically stronger than those with adjacent-rich monomer sequences in water,while hydrogels with a rich cation-πadjacent sequence showed excellent mechanical strength and underwater adhesion in saltwater(0.7 M Na Cl).The molecular mechanisms for these behaviors are discussed in terms of polymer structures.This work reveals the importance of monomeric sequences in determining hydrogel properties and provides a facile approach to develop hydrogels with different properties but the same monomer composition.
基金supported by the Japan Society for the Promotion of Science(JSPS)KAKENHI(Grant Nos.JP17H06144 and JP19K23617)the Institute for Chemical Reaction Design and Discovery(ICReDD)established by World Premier International Research Initiative(WPI),MEXT,Japan.
文摘Biological soft tissues and hydrogels belong to the same category of soft and wet matter.Both of them are composed of polymer network and a certain amount of water,and permeable to small molecules.Biological tissues possess elaborated structures and exhibit outstanding functionalities.On the other hand,hydrogels are usually amorphous with poor functionality.In recent years,various hydrogels with robust functionalities have been developed by introducing aggregated structures into the gel networks,widely extend their applications in diverse fields,such as soft actuators,biological sensors,and structural biomaterials.Four strategies are usually used to fabricate aggregated structure into hydrogels,including molecular self-assembling,microphase separation,crystallization,and inorganic additives.Different aggregated structures entail the gel very different functionalities.A simple aggregated structure is able to bring multiple functionalities and a combination of mechanical performances of the hydrogels.In this review,we describe the strategies used to construct aggerated structure in hydrogels and discuss about the close relation between the aggregated structure and functionality.We also highlight the role of nonequilibrium aggregated structure in fabricating hydrogels with dynamic memorizing-forgetting behavior and point out the remaining challenges.
