Intermediate filaments are one of the key components of the cytoskeleton in eukaryotic cells, and their mechanical properties are found to be equally important for physiological function and disease. While the mechani...Intermediate filaments are one of the key components of the cytoskeleton in eukaryotic cells, and their mechanical properties are found to be equally important for physiological function and disease. While the mechanical properties of single full length filaments have been studied, how the mechanical properties of crosslinks affect the mechanical property of the intermediate filament network is not well understood. This paper applies a mesoscopic model of the intermediate network with varied crosslink strengths to investigate its failure mechanism under the extreme mechanical loading. It finds that relatively weaker crosslinks lead to a more flaw tolerant intermediate filament network that is also 23% stronger than the one with strong crosslinks. These findings suggest that the mechanical properties of interfacial components are critical for bioinspired designs which provide intriguing mechanical properties.展开更多
Intermediate filaments, in addition to microtubules and actin microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that in most cel...Intermediate filaments, in addition to microtubules and actin microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that in most cells, intermediate filament proteins play key roles to reinforce cells subjected to large-deformation, and that they participate in signal transduction, and it was proposed that their nanome- chanical properties are critical to perform those functions. However, it is still poorly understood how the nanoscopic structure, as well as the combination of chemical composition, molecular structure and interfacial properties of these protein molecules contribute to the biomechanical properties of filaments and filament networks. Here we review recent progress in computational and theoretical studies of the intermediate filaments network at various levels in the protein's structure. A multiple scale method is discussed, used to couple molecular modeling with atomistic detail to larger-scale material properties of the networked material. It is shown that a finer-trains-coarser method- ology as discussed here provides a useful tool in understanding the biomechanical property and disease mechanism of intermediate filaments, coupling experiment and simulation. It further allows us to improve the understanding of associated disease mechanisms and lays the foundation for engineering the mechanical properties of biomaterials.展开更多
Podocytes in renal glomemlus express unusual intermediate filament proteins (IFs) for visceral epithelial cells. IFs cytoskeleton is mainly composed of vimentin, nestin and desmin. Tissue injury is often accompanied...Podocytes in renal glomemlus express unusual intermediate filament proteins (IFs) for visceral epithelial cells. IFs cytoskeleton is mainly composed of vimentin, nestin and desmin. Tissue injury is often accompanied by changes in gene expression of IFs. Enhanced desmin staining in variety of rat experimental including 2 4 puromycin nephrosis. It has not podocytes are observed in a models of podocyte injury aminonucleoside (PAN) been elucidated whether expression of vimentin and nestin is up-regulated in podocyte injury. To further gain insight into expression of IFs in podocytes, we investigated the time course of vimentin, nestin and desmin in PAN nephrosis.展开更多
Bone morphogenetic protein-7 is widely accepted as an inducer for bone marrow stem cells differentiating into osteoblasts and chondrocytes. Whether bone marrow stromal cells differentiate into neuron-like cells remain...Bone morphogenetic protein-7 is widely accepted as an inducer for bone marrow stem cells differentiating into osteoblasts and chondrocytes. Whether bone marrow stromal cells differentiate into neuron-like cells remains unclear. The current study examined the presence of positive cells for intermediate filament protein and microtubule associated protein-2 in the cytoplasm of bone marrow stromal cells induced by bone morphogenetic protein-7 under an inverted microscope, while no expression of glial fibrillary acidic protein was found. Reverse transcription PCR electrophoresis also revealed a positive target band for intermediate filament protein and microtubule-associated protein 2 mRNA. These results confirmed that bone morphogenetic protein-7 induces rat bone marrow stromal cells differentiating into neuron-like cells.展开更多
The global economy and public health are currently under enormous pressure since the outbreak of COVID-19. Apart from respiratory discomfort, a subpopulation of COVID-19 patients exhibits neurological symptoms such as...The global economy and public health are currently under enormous pressure since the outbreak of COVID-19. Apart from respiratory discomfort, a subpopulation of COVID-19 patients exhibits neurological symptoms such as headache, myalgia, and loss of smell. Some have even shown encephalitis and necrotizing hemorrhagic encephalopathy. The cytoskeleton of nerve cells changes drastically in these pathologies, indicating that the cytoskeleton and its related proteins are closely related to the pathogenesis of nervous system diseases. In this review, we present the up-to-date association between host cytoskeleton and coronavirus infection in the context of the nervous system. We systematically summarize cytoskeleton-related pathogen-host interactions in both the peripheral and central nervous systems, hoping to contribute to the development of clinical treatment in COVID-19 patients.展开更多
Background Intermediate filament (IF) proteins have been thought to play a role in nuclear centration, organelle movement and maintenance of cell shape, dl-praeruptorin A (Pd-la), a novel Ca^2+-influx blocker and...Background Intermediate filament (IF) proteins have been thought to play a role in nuclear centration, organelle movement and maintenance of cell shape, dl-praeruptorin A (Pd-la), a novel Ca^2+-influx blocker and K^+-channel opener isolated from Chinese traditional herbal medicine Qian-Hu, has been demonstrated to inhibit expression of apoptosis related proteins and reduce the level of proinflammatory factors in ischemia/reperfusion myocardiocytes. Morphologically, whether Pd-la effects myocardiocyte IFs remains unclear. The purpose of this study was, for the first time, to evaluate the in vivo effects of Pd-la on IF desmin and vimentin content in order to further explore its cardioprotection against ischemia and elucidate its mechanism of action. Methods Rats underwent a 30 minutes coronary occlusion followed by 120 minutes reperfusion. Assessment of desmin and vimentin content of myocardiocytes was performed by immunohistochemistry, Western blot, Hematoxylin-Eosin staining and densitometry. Results Pretreatment with i.v. infusion of Pd-la prior to ischemia significantly increased desmin and vimentin content and alleviated defects caused by the ischemia/reperfusion insult, e.g. with Pd-la at a dose of 0.5 or 1.0 mg/kg, integrated density values of desmin were increased from 61 478 ± 10 074 to 177 408 ±10 395 and 195 784±20 057, and vimentin from 59 189± 19 853 to 164 781± 19 543 and 185 696± 20 957 (P〈0.01, vs placebo), respectively. The recovery of desmin seemed to be stronger and appeared earlier than that of vimentin. Conclusion Pd-la protectively increased IF desmin and vimentin content in ischemia/reperfusion myocardiocytes, which might be partially responsible for its cardioprotection against ischemia.展开更多
The neuronal cytoskeleton not only provides the structural backbone of neurons, but also plays a fundamental role in maintaining neuronal functions. Dysregulation of neuronal architecture is evident in both injury and...The neuronal cytoskeleton not only provides the structural backbone of neurons, but also plays a fundamental role in maintaining neuronal functions. Dysregulation of neuronal architecture is evident in both injury and diseases of the central nervous system. These changes often result in the disruption of protein trafficking, loss of synapses and the death of neurons, ultimately impacting on signal transmission and manifesting in the disease phenotype. Furthermore, mutations in cytoskeletal proteins have been implicated in numerous diseases and, in some cases, identified as the cause of the disease, highlighting the critical role of the cytoskeleton in disease pathology. This review focuses on the role of cytoskeletal proteins in the pathology of mental disorders, neurodegenerative diseases and motor function deficits. In particular, we illustrate how cytoskeletal proteins can be directly linked to disease pathology and progression.展开更多
The emerging coronavirus(CoV)pandemic is threatening the public health all over the world.Cytoskeleton is an intricate network involved in controlling cell shape,cargo transport,signal transduction,and cell division.I...The emerging coronavirus(CoV)pandemic is threatening the public health all over the world.Cytoskeleton is an intricate network involved in controlling cell shape,cargo transport,signal transduction,and cell division.Infection biology studies have illuminated essential roles for cytoskeleton in mediating the outcome of host-virus interactions.In this review,we discuss the dynamic interactions between actin filaments,microtubules,intermediate filaments,and CoVs.In one round of viral life cycle,CoVs surf along filopodia on the host membrane to the entry sites,utilize specific intermediate filament protein as co-receptor to enter target cells,hijack microtubules for transportation to replication and assembly sites,and promote actin filaments polymerization to provide forces for egress.During CoV infection,disruption of host cytoskeleton homeostasis and modification state is tightly connected to pathological processes,such as defective cytokinesis,demyelinating,cilia loss,and neuron necrosis.There are increasing mechanistic studies on cytoskeleton upon CoV infection,such as viral protein-cytoskeleton interaction,changes in the expression and post-translation modification,related signaling pathways,and incorporation with other host factors.Collectively,these insights provide new concepts for fundamental virology and the control of CoV infection.展开更多
The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment;however,biocompatibility and targeted penetration of these nanomaterials remain as limitations,which lead to...The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment;however,biocompatibility and targeted penetration of these nanomaterials remain as limitations,which lead to serious side effects and significantly narrow the scope of their application.The self-assembly of intermediate filaments with arginine-glycine-aspartate(RGD)peptide(RGDIFP)was triggered by the hydrophobic cationic molecule 7-amino actinomycin D(7-AAD)to synthesize a bifunctional nanoparticle that could serve as a fluorescent imaging probe to visualize tumor treatment.The designed RGD-IFP peptide possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method.This fluorescent nanoprobe with RGD peptide could be targeted for delivery into tumor cells and released in acidic environments such as endosomes/lysosomes,ultimately inducing cytotoxicity by arresting tumor cell cycling with inserted DNA.It is noteworthy that the RGD-IFP/7-AAD nanoprobe tail-vein injection approach demonstrated not only high tumor-targeted imaging potential,but also potent antitumor therapeutic effects in vivo.The proposed strategy may be used in peptide-driven bifunctional nanoparticles for precise imaging and cancer therapy.展开更多
文摘Intermediate filaments are one of the key components of the cytoskeleton in eukaryotic cells, and their mechanical properties are found to be equally important for physiological function and disease. While the mechanical properties of single full length filaments have been studied, how the mechanical properties of crosslinks affect the mechanical property of the intermediate filament network is not well understood. This paper applies a mesoscopic model of the intermediate network with varied crosslink strengths to investigate its failure mechanism under the extreme mechanical loading. It finds that relatively weaker crosslinks lead to a more flaw tolerant intermediate filament network that is also 23% stronger than the one with strong crosslinks. These findings suggest that the mechanical properties of interfacial components are critical for bioinspired designs which provide intriguing mechanical properties.
文摘Intermediate filaments, in addition to microtubules and actin microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that in most cells, intermediate filament proteins play key roles to reinforce cells subjected to large-deformation, and that they participate in signal transduction, and it was proposed that their nanome- chanical properties are critical to perform those functions. However, it is still poorly understood how the nanoscopic structure, as well as the combination of chemical composition, molecular structure and interfacial properties of these protein molecules contribute to the biomechanical properties of filaments and filament networks. Here we review recent progress in computational and theoretical studies of the intermediate filaments network at various levels in the protein's structure. A multiple scale method is discussed, used to couple molecular modeling with atomistic detail to larger-scale material properties of the networked material. It is shown that a finer-trains-coarser method- ology as discussed here provides a useful tool in understanding the biomechanical property and disease mechanism of intermediate filaments, coupling experiment and simulation. It further allows us to improve the understanding of associated disease mechanisms and lays the foundation for engineering the mechanical properties of biomaterials.
基金a Grant-in-Aid for Scientific Research (C) from the Japanese Ministry for Education, Culture,Sports, Science and Technology (No. 17590822).
文摘Podocytes in renal glomemlus express unusual intermediate filament proteins (IFs) for visceral epithelial cells. IFs cytoskeleton is mainly composed of vimentin, nestin and desmin. Tissue injury is often accompanied by changes in gene expression of IFs. Enhanced desmin staining in variety of rat experimental including 2 4 puromycin nephrosis. It has not podocytes are observed in a models of podocyte injury aminonucleoside (PAN) been elucidated whether expression of vimentin and nestin is up-regulated in podocyte injury. To further gain insight into expression of IFs in podocytes, we investigated the time course of vimentin, nestin and desmin in PAN nephrosis.
基金Science and Technology Research and Development Program of Shihezi University, No. ZRKX2009YB23
文摘Bone morphogenetic protein-7 is widely accepted as an inducer for bone marrow stem cells differentiating into osteoblasts and chondrocytes. Whether bone marrow stromal cells differentiate into neuron-like cells remains unclear. The current study examined the presence of positive cells for intermediate filament protein and microtubule associated protein-2 in the cytoplasm of bone marrow stromal cells induced by bone morphogenetic protein-7 under an inverted microscope, while no expression of glial fibrillary acidic protein was found. Reverse transcription PCR electrophoresis also revealed a positive target band for intermediate filament protein and microtubule-associated protein 2 mRNA. These results confirmed that bone morphogenetic protein-7 induces rat bone marrow stromal cells differentiating into neuron-like cells.
基金supported by Key Research and Development Program,Ministry of Science and Technology of China(Grant Nos.2022YFC2303502 and 2021YFC2300204)CAS-VPST Silk Road Science Fund(Grant No.GJHZ2021138).
文摘The global economy and public health are currently under enormous pressure since the outbreak of COVID-19. Apart from respiratory discomfort, a subpopulation of COVID-19 patients exhibits neurological symptoms such as headache, myalgia, and loss of smell. Some have even shown encephalitis and necrotizing hemorrhagic encephalopathy. The cytoskeleton of nerve cells changes drastically in these pathologies, indicating that the cytoskeleton and its related proteins are closely related to the pathogenesis of nervous system diseases. In this review, we present the up-to-date association between host cytoskeleton and coronavirus infection in the context of the nervous system. We systematically summarize cytoskeleton-related pathogen-host interactions in both the peripheral and central nervous systems, hoping to contribute to the development of clinical treatment in COVID-19 patients.
基金This study was partly supported by a grant from the Key Foundation of Ministry of Public Health of China(No.88402257)
文摘Background Intermediate filament (IF) proteins have been thought to play a role in nuclear centration, organelle movement and maintenance of cell shape, dl-praeruptorin A (Pd-la), a novel Ca^2+-influx blocker and K^+-channel opener isolated from Chinese traditional herbal medicine Qian-Hu, has been demonstrated to inhibit expression of apoptosis related proteins and reduce the level of proinflammatory factors in ischemia/reperfusion myocardiocytes. Morphologically, whether Pd-la effects myocardiocyte IFs remains unclear. The purpose of this study was, for the first time, to evaluate the in vivo effects of Pd-la on IF desmin and vimentin content in order to further explore its cardioprotection against ischemia and elucidate its mechanism of action. Methods Rats underwent a 30 minutes coronary occlusion followed by 120 minutes reperfusion. Assessment of desmin and vimentin content of myocardiocytes was performed by immunohistochemistry, Western blot, Hematoxylin-Eosin staining and densitometry. Results Pretreatment with i.v. infusion of Pd-la prior to ischemia significantly increased desmin and vimentin content and alleviated defects caused by the ischemia/reperfusion insult, e.g. with Pd-la at a dose of 0.5 or 1.0 mg/kg, integrated density values of desmin were increased from 61 478 ± 10 074 to 177 408 ±10 395 and 195 784±20 057, and vimentin from 59 189± 19 853 to 164 781± 19 543 and 185 696± 20 957 (P〈0.01, vs placebo), respectively. The recovery of desmin seemed to be stronger and appeared earlier than that of vimentin. Conclusion Pd-la protectively increased IF desmin and vimentin content in ischemia/reperfusion myocardiocytes, which might be partially responsible for its cardioprotection against ischemia.
文摘The neuronal cytoskeleton not only provides the structural backbone of neurons, but also plays a fundamental role in maintaining neuronal functions. Dysregulation of neuronal architecture is evident in both injury and diseases of the central nervous system. These changes often result in the disruption of protein trafficking, loss of synapses and the death of neurons, ultimately impacting on signal transmission and manifesting in the disease phenotype. Furthermore, mutations in cytoskeletal proteins have been implicated in numerous diseases and, in some cases, identified as the cause of the disease, highlighting the critical role of the cytoskeleton in disease pathology. This review focuses on the role of cytoskeletal proteins in the pathology of mental disorders, neurodegenerative diseases and motor function deficits. In particular, we illustrate how cytoskeletal proteins can be directly linked to disease pathology and progression.
基金This study was supported by Shanghai Municipal Science and Technology Major Project(20431900402 and 2019SHZDZX02)the National Natural Science Foundation of China(31970660)+3 种基金Natural Science Foundation of Shanghai(19ZR1463000)Chemical Reagent Instrumental Development Foundation of Shanghai(1914200700)‘100 Talents Program’from the Chinese Academy of SciencesShanghai Talent Development Funding.
文摘The emerging coronavirus(CoV)pandemic is threatening the public health all over the world.Cytoskeleton is an intricate network involved in controlling cell shape,cargo transport,signal transduction,and cell division.Infection biology studies have illuminated essential roles for cytoskeleton in mediating the outcome of host-virus interactions.In this review,we discuss the dynamic interactions between actin filaments,microtubules,intermediate filaments,and CoVs.In one round of viral life cycle,CoVs surf along filopodia on the host membrane to the entry sites,utilize specific intermediate filament protein as co-receptor to enter target cells,hijack microtubules for transportation to replication and assembly sites,and promote actin filaments polymerization to provide forces for egress.During CoV infection,disruption of host cytoskeleton homeostasis and modification state is tightly connected to pathological processes,such as defective cytokinesis,demyelinating,cilia loss,and neuron necrosis.There are increasing mechanistic studies on cytoskeleton upon CoV infection,such as viral protein-cytoskeleton interaction,changes in the expression and post-translation modification,related signaling pathways,and incorporation with other host factors.Collectively,these insights provide new concepts for fundamental virology and the control of CoV infection.
基金supported by the National Natural Science Foundation of China(No.81603016,81773624,81900453)the Natural Science Foundation of Jiangsu Province(No.BK20160706,BE2017746,China)the National Science and Technology Major Project(2018ZX09301026-005,2020ZX09201015,China)。
文摘The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment;however,biocompatibility and targeted penetration of these nanomaterials remain as limitations,which lead to serious side effects and significantly narrow the scope of their application.The self-assembly of intermediate filaments with arginine-glycine-aspartate(RGD)peptide(RGDIFP)was triggered by the hydrophobic cationic molecule 7-amino actinomycin D(7-AAD)to synthesize a bifunctional nanoparticle that could serve as a fluorescent imaging probe to visualize tumor treatment.The designed RGD-IFP peptide possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method.This fluorescent nanoprobe with RGD peptide could be targeted for delivery into tumor cells and released in acidic environments such as endosomes/lysosomes,ultimately inducing cytotoxicity by arresting tumor cell cycling with inserted DNA.It is noteworthy that the RGD-IFP/7-AAD nanoprobe tail-vein injection approach demonstrated not only high tumor-targeted imaging potential,but also potent antitumor therapeutic effects in vivo.The proposed strategy may be used in peptide-driven bifunctional nanoparticles for precise imaging and cancer therapy.