Nanoparticles have been widely applied in diagnosis and therapy due to the high loading of insoluble drug, increased target accumulation and interaction with biological tissues. Recently, severe side effects of nanopa...Nanoparticles have been widely applied in diagnosis and therapy due to the high loading of insoluble drug, increased target accumulation and interaction with biological tissues. Recently, severe side effects of nanoparticles have been reported, but the underlying mechanism remains largely unknown. In our study, we aim to understand the safety of paclitaxel （PTX） loaded bovine albumin nanoparticles （BNPs） and active targeted PTX loaded BNPs to normal vital organ or tissue in vivo. The anti-human epidermal growth factor receptor 2 （HER2/neu） peptide mimetic （AHNP） was covalent bound to surface of BNPs （AHNP-BNPs） to exert selected delivery to HER2＋ cells. In HER2＋ tumor xenographs, saline （control）, PTX traditional formula （medium of Cremophor EL-ethanol）, BNPs, and AHNP-BNPs were administrated to evaluate the toxicity. There is no severe neutropenia or anemia with treatment of BNPs and AHNP-BNPs compared with traditional PTX injection. We also evaluated their damage on normal organs, including liver, kidney, spleen, lung and heart to fully estimate the safety of AHNP-BNPs and BNPs delivery systems. We observed similar toxicity in liver and lung in mice treated with BNPs or PTX injection, but decreased liver damage in mice treated with AHNP-BNPs. Further studies are rcouired to confirm our conclusion.展开更多
Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially...Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially in some patients with organ failure.^(2)Therefore,“exercise pills”and“exercise mimetics”have attracted growing interest because of their potential to induce exercise-related health effects despite physical exercise not being performed.^(3)Robust studies over the past decade have identified many natural biomacromolecules,such as peptide,non-coding Ribonucleic Acid(RNAs),and lipids,that are induced by exercise.^(4-6)These molecules trigger physiological adaptations,including promotion of cardiomyocyte proliferation,anti-apoptotic capacity,and healthy tissue growth.7However,identifying or designing an exercise pill that mimics the extensive benefits of exercise is still challenging.展开更多
Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(...Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(6'-SL),which is known to beneficially influence neural functions.Using Sambucus nigra lectin,which specifically binds to 6'-SL,we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids.Mimetic peptide,reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin.Indeed,lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide,but not by the reverse or scrambled peptides,showing that this peptide mimics 6'-SL.Functionally,mimetic peptide,but not the reverse or scrambled peptides,increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells,and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H_20_2-induced oxidative stress.The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis,thus raising hopes for the treatment of neurodegenerative diseases.This study was approved by the Medical Ethics Committee of Shantou University Medical College,China(approval No.SUMC 2014-004)on February 20,2014.展开更多
Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-ad...Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-adhesion hydrogels combined with growth factors is a promising strategy to address endometrial injury.Insulin-like growth factor 1 is closely associated with endometrial growth and plays a crucial role in endometrial receptivity that is essential for fertility.However,its high cost,environmental sensitivity,and short biological half-life limit its practical applications.In this study,we developed a two-component peptide-based hydrogel consisting of a biotinylated peptide and an insulin-like growth factor 1(IGF-1)mimetic peptide,both of which were designed with self-assembly capabilities.The resultant hydrogel exhibited significant mechanical properties and retained its native IGF-1 bioactivity.In vivo experiments demonstrated that the hydrogel significantly facilitated proliferation and vascular restoration.Additionally,it effectively reduced fibrosis by decreasing collagen accumulation,restoring the expression of progesterone receptors,and enhancing endometrial receptivity,which are crucial for embryo implantation.These findings highlight the potential of the two-component peptide-based hydrogel as an innovative therapeutic approach for treating endometrial injury.展开更多
Insulin is a protein hormone secreted by pancreatic β cells. One of its main functions is to keep the balance of glucose inside the body by regulating the absorption and metabolism of glucose in the periphery tissue,...Insulin is a protein hormone secreted by pancreatic β cells. One of its main functions is to keep the balance of glucose inside the body by regulating the absorption and metabolism of glucose in the periphery tissue, as well as the production and storage of hepatic glycogen. The insulin receptor is a transmembrane glycoprotein in which two a subunits with a molecular weight of 135 kD and two,8 subunits with a molecular weight of 95 kD are joined by a disulfide bond to form a β-α-α-β structure. The extracellular a subunit, especially, its three domains near the N-terminal are partially responsible for signal transduction or ligand-binding, as indicated by the experiments. The extracellular α subunits are involved in binding the ligands. The experimental results indicate that the three domains of the N-terminal of the a subunits are the main determinative parts of the insulin receptor to bind the insulin or mimetic peptide. We employed the extracellular domain（ PDBID： 1IGR） of the insulin-like growth factor-1 receptor （IGF-1R） as the template to simulate and optimize the spatial structures of the three domains in the extracellular domain of the insulin receptor, which includes 468 residues. The work was accomplished by making use of the homology program in the Insight Ⅱ package on an Origin3800 server. The docking calculations of the insulin receptor obtained by homology with hexapeptides were carried out by means of the program Affinity. The analysis indicated that there were hydrogen bonding, and electrostatic and hydrophobic effects in the docking complex of the insulin receptor with hexapeptides. Moreover, we described the spatial orientation of a mimetic peptide with agonist activity in the docking complex. We obtained a rough model of binding of DLAPSQ or STIVYS with the insulin receptor, which provides the powerful theoretical support for designing the minimal insulin mimetic peptide with agonist activity, making it possible to develop oral small molecular hypoglycemic drugs.展开更多
Skin aging,a complex physiological process characterized by alterations in skin structure and function,seriously affects human life.Collagen holds considerable potential in aging skin treatment,while animal-derived co...Skin aging,a complex physiological process characterized by alterations in skin structure and function,seriously affects human life.Collagen holds considerable potential in aging skin treatment,while animal-derived collagen poses risks of pathogen transmission.Self-assembled peptides have garnered increasing attention in creating collagen mimetic materials;however,previous reported self-assembled peptides rely on vulnerable non-covalent interactions or lack the capability of controlling morphology and incorporating functional motifs,limiting their ability to mimic collagen structure and function.We have herein created a controllable tyrosine-rich triblock peptide system capable of self-assembling into robust collagen mimetic bioscaffolds for rejuvenating aging skin.Through ruthenium-mediated crosslinking,these peptides self-assemble into well-defined nanospheres or collagen-mimetic scaffolds,precisely regulated by the triple-helical structure and tyrosine distribution.The self-assembled collagen mimetic scaffolds exhibit outstanding resistances to various solvents and pH conditions.The integrin-binding motif has been incorporated into the triple helical block without disrupting their assembly,while endowing them with superior bioactivities,effectively promoting cell adhesion and proliferation.In vivo studies demonstrated their efficacy in treating photoaging skin by accelerating collagen regeneration and activating fibroblasts.The self-assembled tyrosine-rich triblock peptides represent a versatile system for creating robust collagen mimetic biomaterials,providing great potential in skin rejuvenation and tissue regeneration.展开更多
Angiogenesis plays an important role in brain injury repair,which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area.As a major component of deve...Angiogenesis plays an important role in brain injury repair,which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area.As a major component of developing brain extracellular matrix,hyaluronic acid(HA)has attracted more attention as a supporting matrix for brain repair.In the present study,HA-KLT hydrogel was developed via modifying HA with a VEGF mimetic peptide of KLT(KLTWQELYQLKYKGI).The characterization of the hydrogel shows that it could provide a porous,three-dimensional scaffold structure,which has a large specific surface area available for cell adhesion and interaction.Compared with the unmodified HA hydrogel,the HA-KLT hydrogel could effectively promote the attachment,spreading and proliferation of endothelial cells in vitro.Furthermore,the pro-angiogenic ability of hydrogels in vivo was evaluated by implanting them into the lesion cavities in the injured rat brain.Our results showed that the hydrogels could form a permissive interface with the host tissues at 4 weeks after implantation.Moreover,they could efficiently inhibit the formation of glial scars at the injured sites.The HA-KLT hydrogel could significantly increase the expression of endoglin/CD105 and promote the formation of blood vessels,suggesting that HA-KLT hydrogel promoted angiogenesis in vivo.Collectively,the HA-KLT hydrogel has the potential to repair brain defects by promoting angiogenesis and inhibiting the formation of glial-derived scar tissue.展开更多
Peptide self-assembles with bionic properties have been widely utilized for bioactive drugs and biomedical materials.Collagen mimetic peptide(CMP)gains more attention due to its unique advantages in biosecurity and fu...Peptide self-assembles with bionic properties have been widely utilized for bioactive drugs and biomedical materials.Collagen mimetic peptide(CMP)gains more attention due to its unique advantages in biosecurity and function.Unfortunately,the self-assembly mechanism of CMP,particularly the effect of intermolecular forces on its self-assembly behavior and morphology,is still unrecognized.Herein,the hydrophilic glycidol(GCD)and hydrophobic Y-glycidyl ether oxypropyl trimethoxysilane(GLH)were grafted onto the side chains of CMP through the ring-opening reaction(GCD/CMP,GLH/CMP).Subsequently,the effects of hydrophilic and hydrophobic interactions on the self-assembly behavior and morphology of CMP were further studied.The results substantiated that the GCD/CMP and GLH/CMP self-assembly followed“nucleation-growth”mechanism,and the supererogatory hydrophilic and hydrophobic groups prolonged the nucleation and growth time of CMP self-assembly.Noted that the hydrophilic interaction had stronger driving effects than hydrophobic interaction on the self-assembly of CMP.The GCD/CMP and GLH/CMP self-assembles exhibited fibrous 3D network and microsphere morphology,respectively.Furthermore,the GLH/CMP self-assembles had better resistance to degradation.Consequently,the microtopography and degradation properties of CMP self-assembles could be controlled by the hydrophilic and hydrophobic interactions between CMP,which would further provide a way for subsequent purposeful design of biomedical materials.展开更多
A new type of collagen mimetic peptide, （PKG）n（POG）2n（DOG）n, with charged-domain ends had been designed and successfully prepared in this work, which self-assembled into collagen-like triple helices homotrimers....A new type of collagen mimetic peptide, （PKG）n（POG）2n（DOG）n, with charged-domain ends had been designed and successfully prepared in this work, which self-assembled into collagen-like triple helices homotrimers. The collagen-like homo- trimers underwent higher level of self-assembly via static electrical interaction between positive and negative domains. Transmission electron microscope （TEM） examinations showed three typical morphologies of homotrimer assembly, which were defined as film, bicontinuous and fibril morphology in this paper. The film was formed in the initial stage and gradually transformed to bicontinuous or fibril morphology to improve stability of the assemblies or decrease surface energy. Furthermore, mechanism of assembly process was proposed based on TEM observations and theoretical analyses of packing equation.展开更多
基金the National Natural Science Foundation of China(Grant No.30970785,81273454)Beijing Natural Science Foundation(Grant No.7132113)+2 种基金National Basic Research Program(Grant No.2009CB930303,2013CB932501)Doctoral Foundation of the Ministry of Education(Grant No.20100001110056)Innovation Team of Ministry of Education(Grant No.BMU20110263)
文摘Nanoparticles have been widely applied in diagnosis and therapy due to the high loading of insoluble drug, increased target accumulation and interaction with biological tissues. Recently, severe side effects of nanoparticles have been reported, but the underlying mechanism remains largely unknown. In our study, we aim to understand the safety of paclitaxel （PTX） loaded bovine albumin nanoparticles （BNPs） and active targeted PTX loaded BNPs to normal vital organ or tissue in vivo. The anti-human epidermal growth factor receptor 2 （HER2/neu） peptide mimetic （AHNP） was covalent bound to surface of BNPs （AHNP-BNPs） to exert selected delivery to HER2＋ cells. In HER2＋ tumor xenographs, saline （control）, PTX traditional formula （medium of Cremophor EL-ethanol）, BNPs, and AHNP-BNPs were administrated to evaluate the toxicity. There is no severe neutropenia or anemia with treatment of BNPs and AHNP-BNPs compared with traditional PTX injection. We also evaluated their damage on normal organs, including liver, kidney, spleen, lung and heart to fully estimate the safety of AHNP-BNPs and BNPs delivery systems. We observed similar toxicity in liver and lung in mice treated with BNPs or PTX injection, but decreased liver damage in mice treated with AHNP-BNPs. Further studies are rcouired to confirm our conclusion.
基金supported by the National Key Research and Development Project(2022YFA1104500 to JX)the National Natural Science Foundation of China(82020108002 and82225005 to JX and 82370277 to HW)+1 种基金the Science and Technology Commission of Shanghai Municipality(23ZR1422900 to HW and 23410750100 to JX)supported by a Biotechnology and Biological Sciences Research Council(BBSRC)International Partnering Award。
文摘Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially in some patients with organ failure.^(2)Therefore,“exercise pills”and“exercise mimetics”have attracted growing interest because of their potential to induce exercise-related health effects despite physical exercise not being performed.^(3)Robust studies over the past decade have identified many natural biomacromolecules,such as peptide,non-coding Ribonucleic Acid(RNAs),and lipids,that are induced by exercise.^(4-6)These molecules trigger physiological adaptations,including promotion of cardiomyocyte proliferation,anti-apoptotic capacity,and healthy tissue growth.7However,identifying or designing an exercise pill that mimics the extensive benefits of exercise is still challenging.
基金supported by the National Natural Science Foundation of China,No.81471279 and No.81171138(to WJZ)Talent Support Grant from Shantou University Medical College,China,No.2501220118(to WJZ)the Li Kashing Foundation,No.LD030302(to MS)
文摘Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(6'-SL),which is known to beneficially influence neural functions.Using Sambucus nigra lectin,which specifically binds to 6'-SL,we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids.Mimetic peptide,reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin.Indeed,lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide,but not by the reverse or scrambled peptides,showing that this peptide mimics 6'-SL.Functionally,mimetic peptide,but not the reverse or scrambled peptides,increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells,and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H_20_2-induced oxidative stress.The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis,thus raising hopes for the treatment of neurodegenerative diseases.This study was approved by the Medical Ethics Committee of Shantou University Medical College,China(approval No.SUMC 2014-004)on February 20,2014.
基金the financial support from the Zhejiang Provincial Natural Science Foundation of China(No.LBY24H040012)Discipline Cluster of Oncology of Wenzhou Medical University(No.z1-2023007)+1 种基金the financial support from the National Natural Science Foundation of China(No.32401107)the financial support from the Discipline Cluster of Oncology of Wenzhou Medical University(No.z3-2023027)。
文摘Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-adhesion hydrogels combined with growth factors is a promising strategy to address endometrial injury.Insulin-like growth factor 1 is closely associated with endometrial growth and plays a crucial role in endometrial receptivity that is essential for fertility.However,its high cost,environmental sensitivity,and short biological half-life limit its practical applications.In this study,we developed a two-component peptide-based hydrogel consisting of a biotinylated peptide and an insulin-like growth factor 1(IGF-1)mimetic peptide,both of which were designed with self-assembly capabilities.The resultant hydrogel exhibited significant mechanical properties and retained its native IGF-1 bioactivity.In vivo experiments demonstrated that the hydrogel significantly facilitated proliferation and vascular restoration.Additionally,it effectively reduced fibrosis by decreasing collagen accumulation,restoring the expression of progesterone receptors,and enhancing endometrial receptivity,which are crucial for embryo implantation.These findings highlight the potential of the two-component peptide-based hydrogel as an innovative therapeutic approach for treating endometrial injury.
文摘Insulin is a protein hormone secreted by pancreatic β cells. One of its main functions is to keep the balance of glucose inside the body by regulating the absorption and metabolism of glucose in the periphery tissue, as well as the production and storage of hepatic glycogen. The insulin receptor is a transmembrane glycoprotein in which two a subunits with a molecular weight of 135 kD and two,8 subunits with a molecular weight of 95 kD are joined by a disulfide bond to form a β-α-α-β structure. The extracellular a subunit, especially, its three domains near the N-terminal are partially responsible for signal transduction or ligand-binding, as indicated by the experiments. The extracellular α subunits are involved in binding the ligands. The experimental results indicate that the three domains of the N-terminal of the a subunits are the main determinative parts of the insulin receptor to bind the insulin or mimetic peptide. We employed the extracellular domain（ PDBID： 1IGR） of the insulin-like growth factor-1 receptor （IGF-1R） as the template to simulate and optimize the spatial structures of the three domains in the extracellular domain of the insulin receptor, which includes 468 residues. The work was accomplished by making use of the homology program in the Insight Ⅱ package on an Origin3800 server. The docking calculations of the insulin receptor obtained by homology with hexapeptides were carried out by means of the program Affinity. The analysis indicated that there were hydrogen bonding, and electrostatic and hydrophobic effects in the docking complex of the insulin receptor with hexapeptides. Moreover, we described the spatial orientation of a mimetic peptide with agonist activity in the docking complex. We obtained a rough model of binding of DLAPSQ or STIVYS with the insulin receptor, which provides the powerful theoretical support for designing the minimal insulin mimetic peptide with agonist activity, making it possible to develop oral small molecular hypoglycemic drugs.
基金supported by grants from the National Natural Science Foundation of China(grant nos.22074057,22205089 and 22304066)the Natural Science Foundation of Gansu Province(grant nos.20YF3FA025 and 23JRRA1096)+1 种基金China Postdoctoral Science Foundation(2022M711449)Lanzhou Science and Technology Program Project(2023-3-31).
文摘Skin aging,a complex physiological process characterized by alterations in skin structure and function,seriously affects human life.Collagen holds considerable potential in aging skin treatment,while animal-derived collagen poses risks of pathogen transmission.Self-assembled peptides have garnered increasing attention in creating collagen mimetic materials;however,previous reported self-assembled peptides rely on vulnerable non-covalent interactions or lack the capability of controlling morphology and incorporating functional motifs,limiting their ability to mimic collagen structure and function.We have herein created a controllable tyrosine-rich triblock peptide system capable of self-assembling into robust collagen mimetic bioscaffolds for rejuvenating aging skin.Through ruthenium-mediated crosslinking,these peptides self-assemble into well-defined nanospheres or collagen-mimetic scaffolds,precisely regulated by the triple-helical structure and tyrosine distribution.The self-assembled collagen mimetic scaffolds exhibit outstanding resistances to various solvents and pH conditions.The integrin-binding motif has been incorporated into the triple helical block without disrupting their assembly,while endowing them with superior bioactivities,effectively promoting cell adhesion and proliferation.In vivo studies demonstrated their efficacy in treating photoaging skin by accelerating collagen regeneration and activating fibroblasts.The self-assembled tyrosine-rich triblock peptides represent a versatile system for creating robust collagen mimetic biomaterials,providing great potential in skin rejuvenation and tissue regeneration.
基金the National Natural Science Foundation of China(31771056 and 81200931)the Tsinghua University Initiative Scientific Research Program(20161080091)+1 种基金the 111 Project(B17026)a special fund from Key laboratory of Neurodegenerative diseases,Ministry of Education(PXM2019_026283_000002).
文摘Angiogenesis plays an important role in brain injury repair,which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area.As a major component of developing brain extracellular matrix,hyaluronic acid(HA)has attracted more attention as a supporting matrix for brain repair.In the present study,HA-KLT hydrogel was developed via modifying HA with a VEGF mimetic peptide of KLT(KLTWQELYQLKYKGI).The characterization of the hydrogel shows that it could provide a porous,three-dimensional scaffold structure,which has a large specific surface area available for cell adhesion and interaction.Compared with the unmodified HA hydrogel,the HA-KLT hydrogel could effectively promote the attachment,spreading and proliferation of endothelial cells in vitro.Furthermore,the pro-angiogenic ability of hydrogels in vivo was evaluated by implanting them into the lesion cavities in the injured rat brain.Our results showed that the hydrogels could form a permissive interface with the host tissues at 4 weeks after implantation.Moreover,they could efficiently inhibit the formation of glial scars at the injured sites.The HA-KLT hydrogel could significantly increase the expression of endoglin/CD105 and promote the formation of blood vessels,suggesting that HA-KLT hydrogel promoted angiogenesis in vivo.Collectively,the HA-KLT hydrogel has the potential to repair brain defects by promoting angiogenesis and inhibiting the formation of glial-derived scar tissue.
基金This work was financially supported by the National Natural Science Foundation of China(21808133)Scientific Research Foundation for Young Scholars of Shaanxi University of Science&Technology(contract grant number 2017BT-32)+1 种基金Xianyang Science and Technology Project(Y20190138)Shaanxi Province Key R&D Program(2018ZDXM-SF-091).
文摘Peptide self-assembles with bionic properties have been widely utilized for bioactive drugs and biomedical materials.Collagen mimetic peptide(CMP)gains more attention due to its unique advantages in biosecurity and function.Unfortunately,the self-assembly mechanism of CMP,particularly the effect of intermolecular forces on its self-assembly behavior and morphology,is still unrecognized.Herein,the hydrophilic glycidol(GCD)and hydrophobic Y-glycidyl ether oxypropyl trimethoxysilane(GLH)were grafted onto the side chains of CMP through the ring-opening reaction(GCD/CMP,GLH/CMP).Subsequently,the effects of hydrophilic and hydrophobic interactions on the self-assembly behavior and morphology of CMP were further studied.The results substantiated that the GCD/CMP and GLH/CMP self-assembly followed“nucleation-growth”mechanism,and the supererogatory hydrophilic and hydrophobic groups prolonged the nucleation and growth time of CMP self-assembly.Noted that the hydrophilic interaction had stronger driving effects than hydrophobic interaction on the self-assembly of CMP.The GCD/CMP and GLH/CMP self-assembles exhibited fibrous 3D network and microsphere morphology,respectively.Furthermore,the GLH/CMP self-assembles had better resistance to degradation.Consequently,the microtopography and degradation properties of CMP self-assembles could be controlled by the hydrophilic and hydrophobic interactions between CMP,which would further provide a way for subsequent purposeful design of biomedical materials.
文摘A new type of collagen mimetic peptide, （PKG）n（POG）2n（DOG）n, with charged-domain ends had been designed and successfully prepared in this work, which self-assembled into collagen-like triple helices homotrimers. The collagen-like homo- trimers underwent higher level of self-assembly via static electrical interaction between positive and negative domains. Transmission electron microscope （TEM） examinations showed three typical morphologies of homotrimer assembly, which were defined as film, bicontinuous and fibril morphology in this paper. The film was formed in the initial stage and gradually transformed to bicontinuous or fibril morphology to improve stability of the assemblies or decrease surface energy. Furthermore, mechanism of assembly process was proposed based on TEM observations and theoretical analyses of packing equation.
