Cell migration in anisotropic microenvironment plays an important role in the development of normal tissues and organs as well as neoplasm progression,e.g.,osteogenic differentiation of embryonic stem cells was facili...Cell migration in anisotropic microenvironment plays an important role in the development of normal tissues and organs as well as neoplasm progression,e.g.,osteogenic differentiation of embryonic stem cells was facilitated on stiffer substrates,indicating that the mechanical signals greatly affect both early and terminal differentiation of embryonic stem cells.However,the effect of anisotropy on cell migration dynamics,in particular,in terms of acceleration profiles which is important for recognizing dynamics modes of cell migration and analyzing the regulation mechanisms of microenvironment in mechanical signal transmission,has not been systematically investigated.In this work,we firstly rigorously investigate and quantify the differences between persistent random walk and anisotropic persistent random walk models based on the analysis of cell migration trajectories and velocity auto-covariance function,both qualitatively and quantitatively.Secondly,we introduce the concepts of positive and negative anisotropy based on the motility parameters to study the effect of anisotropy on acceleration profiles,especially the nonlinear decrease and non-monotonic behaviors.We particularly elaborate and discuss the mechanisms,and physical insights of non-monotonic behaviors in the case of positive anisotropy,focusing on the force exerted on migrating cells.Finally,we analyze two types of in vitro cell migration experiments and verify the universality of nonlinear decrease and the consistence of non-monotonic behaviors with numerical results.We conclude that the anisotropy of microenvironment is the cause of the non-monotonic and nonlinear dynamics,and the anisotropic persistent random walk can be as a suitable tool to analyze in vitro cell migration with different combinations of motility parameters.Our analysis provides new insights into the dynamics of cell migration in complex microenvironment,which also has implications in tissue engineering and cancer research.展开更多
Impacts of microenvironments on cell migration have been reported in various interaction modes.A rapid tumor metastasis occurs along topological interfaces in vivo,such as the interface between the blood vessels and n...Impacts of microenvironments on cell migration have been reported in various interaction modes.A rapid tumor metastasis occurs along topological interfaces in vivo,such as the interface between the blood vessels and nerves.In this work,we culture MDA-MB231 cells at dish-liquid,dish-hydrogel,and hydrogel-liquid interfaces,respectively,to study how these different interfaces influence cell dynamics and morphology.Our results show that the migration mode of cells changes from an amoeboid motion to a mesenchymal motion but their speed do not change obviously if the interface changes from hydrogel-liquid to dish-liquid.In contrast,the migration mode of cells at a dish-hydrogel interface maintains as a mesenchymal motion,whereas their speed increases significantly.展开更多
Studies on pattern formation in coculture cell systems can provide insights into many physiological and pathological processes.Here,we investigate how the extracellular matrix(ECM)may influence the patterning in cocul...Studies on pattern formation in coculture cell systems can provide insights into many physiological and pathological processes.Here,we investigate how the extracellular matrix(ECM)may influence the patterning in coculture systems.The model coculture system we use is composed of highly motile invasive breast cancer cells,initially mixed with inert nonmetastatic cells on a 2D substrate and covered with a Matrigel layer introduced to mimic ECM.We observe that the invasive cells exhibit persistent centripetal motion and yield abnormal aggregation,rather than random spreading,due to a“collective pulling”effect resulting from ECM-mediated transmission of active contractile forces generated by the polarized migration of the invasive cells along the vertical direction.The mechanism we report may open a new window for the understanding of biological processes that involve multiple types of cells.展开更多
SARS-CoV-2 has caused asevere pneumoniapandemic worldwide with high morbidity and mortality.Howto developa preclinical model for recapitulating SARS-CoV-2 pathogenesis is stil urgent and essential for the control of t...SARS-CoV-2 has caused asevere pneumoniapandemic worldwide with high morbidity and mortality.Howto developa preclinical model for recapitulating SARS-CoV-2 pathogenesis is stil urgent and essential for the control of the pandemic.Here,we have established a 3D biomimetic alveolus-on-a-chip with mechanical strain and extracellular matrix taken into consideration.We have validated that the alveolus-on-a-chip is capable of recapitulating key physiological characteristics of human alveolar units,which lays a fundamental basis for viral infection studies at the organ level.Using virus-analogous chemicals and pseudovirus,we have explored virus pathogenesis and blocking ability of antibodies during viral infection.This work provides a favorable platform for SARS-Cov-2-related researches and has a great potential for physiology and pathophysiology studies of the human lung at the organ level in vitro.展开更多
Adsorbents with high adsorption efficiency and excellent biosafety for biomedical applications are highly required.MXene is a promising candidate owning these advantages,yet pristine MXene faces dilemmas including ins...Adsorbents with high adsorption efficiency and excellent biosafety for biomedical applications are highly required.MXene is a promising candidate owning these advantages,yet pristine MXene faces dilemmas including insufficient utility of sur-face site as well as limited processibility.Here,we develop MXene-encapsulated porous microcapsules via microfluidics.The microcapsules have a biomass hydrogel shell that provides robust support for MXene in the core,by which the microcapsules are endowed with high MXene dosage and remarkable biosafety.Additionally,the MXene nanoflakes assemble into a three-dimensional network via metal ion-induced gelation,thereby avoiding restacking and significantly improving surface utiliza-tion.Moreover,a freeze-pretreatment of the microcapsules during preparation results in the formation of a macroporous structure in the shell,which can facilitate the diffusion of the target molecules.These features,combined with additional magneto-responsiveness rendered by the incorporation of magnetic nanoparticles,contribute to prominent performances of the microcapsules in cleaning uremia toxins including creatinine,urea,and uric acid.Thus,it is anticipated that the MXene-encapsulated microcapsules will be promising adsorbents in dialysis-related applications,and the combination of microfluidic encapsulation with metal ion gelation will provide a novel approach for construction of hybrid MXene materials with desired functions.展开更多
Cellular collective motion in confluent epithelial monolayers is involved in many processes such as embryo development,carcinoma invasion,and wound healing.The development of new chemical strategies to achieve largesc...Cellular collective motion in confluent epithelial monolayers is involved in many processes such as embryo development,carcinoma invasion,and wound healing.The development of new chemical strategies to achieve largescale control of cells’collective motion is essential for biomedical applications.Here a series of DNA nanostructures with different dimensions were synthesized and their influences on cells’collective migration and packing behaviors in epithelial monolayers were investigated.We found that the framed DNA nanoassemblies effectively reduced the cells’speed by increasing the rigidity of cells,while the lipid-DNA micelles had a more pronounced effect on cells’projection area and shape factor.These DNA nanostructures all significantly enhanced the dependence of cells’speed on their shape factor.Our results indicate that cells’mobility in monolayers can be manipulated by chemical intercellular interactions without any genetic intervention.This may provide a new chemical strategy for tissue engineering and tumor therapy.展开更多
Microglia are resident macrophage cells in the central nervous system that search for pathogens or abnormal neural activities and migrate to resolve the issues.The effective search and targeted motion of macrophages m...Microglia are resident macrophage cells in the central nervous system that search for pathogens or abnormal neural activities and migrate to resolve the issues.The effective search and targeted motion of macrophages mean dearly to maintaining a healthy brain,yet little is known about their migration dynamics.In this work,we study microglial motion with and without the presence of external mechanostimuli.We discover that the cells are promptly attracted by the applied forces(i.e.,mechanotaxis),which is a tactic behavior as yet unconfirmed in microglia.Meanwhile,in both the explorative and the targeted migration,microglia display dynamics that is strikingly analogous to bacterial run-and-tumble motion.A closer examination reveals that microglial run-and-tumble is more sophisticated,e.g.,they display a short-term memory when tumbling and rely on active steering during runs to achieve mechanotaxis,probably via the responses of mechanosensitive ion channels.These differences reflect the sharp contrast between microglia and bacteria cells(eukaryotes vs.prokaryotes)and their environments(compact tissue vs.fluid).Further analyses suggest that the reported migration dynamics has an optimal search efficiency and is shared among a subset of immune cells(human monocyte and macrophage).This work reveals a fruitful analogy between the locomotion of 2 remote systems and provides a framework for studying immune cells exploring complex environments.展开更多
Studiesonpattern formation in coculturecell systemscan provide insights intomany physiological and pathologicalprocesses Here,we investigate how theextracellular matrix(ECM)may influence the patterning in coculture sy...Studiesonpattern formation in coculturecell systemscan provide insights intomany physiological and pathologicalprocesses Here,we investigate how theextracellular matrix(ECM)may influence the patterning in coculture systems.Themodel coculture system we use is composed of highly motile invasivebreast cancer cells,initially mixed with inert nonmetastatic cells on a 2D substrate and covered with a Matrigel layer introduced to mimic ECM.We observe that the invasive cells exhibit persistent centripetal motion and yield abnormal aggregation,rather than random spreading,due to a“cllective pulling”effect resultingfrom ECM-mediated transmssion of active contractile forces generated bythe polarized migration of the invasive cells along the vertical direction.Themechanism we report may open a new window for the understanding of biological processes that involve multiple types of cells.展开更多
Adsorption or enrichment has been an indispensable and important measure in biomedical engineering since it is promising in diagnosis and treatment of complex diseases.The ongoing development in this arena starves for...Adsorption or enrichment has been an indispensable and important measure in biomedical engineering since it is promising in diagnosis and treatment of complex diseases.The ongoing development in this arena starves for exploration of outstanding adsorptive materials.As an excellent candidate for adsorption or enrichment carriers,carbon-based material has demonstrated unique superiority in biomedical arena owing to its integrated charac-teristics.Herein,we review the lasted advance in adsorptive carbon-based materials for biomedical application with emphasis on carbon nanotubes(CNTs)-based,graphene-based,and biomass/polymer-based ones.We begin with the classification of different carbon-based materials and elaborate the respective preparation approaches that are utilized to realize optimized microstructure and physicochemical property.Afterwards,we introduce the different applications of carbon-based materials in biomedical arena,including blood purification,enrichment of glycopeptide and phosphopeptide,and breath analysis.Finally,we present a concise summary and give an outlook of this arena.展开更多
Primary liver cancer is the fifth most common malignancy and the third leading cause of cancer death worldwide.Although current advances in the treatment of liver cancer,the prognosis of this cancer remains unfavorabl...Primary liver cancer is the fifth most common malignancy and the third leading cause of cancer death worldwide.Although current advances in the treatment of liver cancer,the prognosis of this cancer remains unfavorable.Appropriate liver cancer model in vitro is an important way to study the pathogenesis and drug screening of liver cancer.This review provides a comprehensive summary and discussion on the construction and application of liver cancer models in vitro,in particular hepatocellular carcinoma(HCC).Specifically,after introducing the current methods or techniques for preparing 3D in vitro liver cancer models,this review summarizes the relevant applications of these liver cancer models in vitro,e.g.drug screening,personalized medicine,and other applications.In the end,this review discusses the advantages and disadvantages of the liver cancer models in vitro,and proposes future prospects and research directions.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11974066,11674043,11675134,and 11874310)the Natural Science Foundation of Chongqing,China(Grant Nos.cstc2019jcyj-msxmX0477 and cstc2018jcyjA3679)the Capital Health Development Research Project,China(Grant No.2020-2-2072).
文摘Cell migration in anisotropic microenvironment plays an important role in the development of normal tissues and organs as well as neoplasm progression,e.g.,osteogenic differentiation of embryonic stem cells was facilitated on stiffer substrates,indicating that the mechanical signals greatly affect both early and terminal differentiation of embryonic stem cells.However,the effect of anisotropy on cell migration dynamics,in particular,in terms of acceleration profiles which is important for recognizing dynamics modes of cell migration and analyzing the regulation mechanisms of microenvironment in mechanical signal transmission,has not been systematically investigated.In this work,we firstly rigorously investigate and quantify the differences between persistent random walk and anisotropic persistent random walk models based on the analysis of cell migration trajectories and velocity auto-covariance function,both qualitatively and quantitatively.Secondly,we introduce the concepts of positive and negative anisotropy based on the motility parameters to study the effect of anisotropy on acceleration profiles,especially the nonlinear decrease and non-monotonic behaviors.We particularly elaborate and discuss the mechanisms,and physical insights of non-monotonic behaviors in the case of positive anisotropy,focusing on the force exerted on migrating cells.Finally,we analyze two types of in vitro cell migration experiments and verify the universality of nonlinear decrease and the consistence of non-monotonic behaviors with numerical results.We conclude that the anisotropy of microenvironment is the cause of the non-monotonic and nonlinear dynamics,and the anisotropic persistent random walk can be as a suitable tool to analyze in vitro cell migration with different combinations of motility parameters.Our analysis provides new insights into the dynamics of cell migration in complex microenvironment,which also has implications in tissue engineering and cancer research.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11774394 and 11704404)the Chinese Academy of Sciences(CAS),and the Key Research Program of Frontier Sciences of CAS(Grant No.QYZDB-SSW-SYS003).
文摘Impacts of microenvironments on cell migration have been reported in various interaction modes.A rapid tumor metastasis occurs along topological interfaces in vivo,such as the interface between the blood vessels and nerves.In this work,we culture MDA-MB231 cells at dish-liquid,dish-hydrogel,and hydrogel-liquid interfaces,respectively,to study how these different interfaces influence cell dynamics and morphology.Our results show that the migration mode of cells changes from an amoeboid motion to a mesenchymal motion but their speed do not change obviously if the interface changes from hydrogel-liquid to dish-liquid.In contrast,the migration mode of cells at a dish-hydrogel interface maintains as a mesenchymal motion,whereas their speed increases significantly.
基金supported by the National Natural Science Foundation of China(Grant Nos.11774394,11974066,12074407,and 12090054)the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB33000000)+2 种基金the Start-Up Fund and University Graduate Fellowship of Arizona State University,the Natural Science Foundation of Chongqing Municipal Science and Technology Commission(Grant No.cstc2019jcyj-msxmX0477)the Fundamental Research Funds for the Central Universities(Grant No.2019CDYGYB007)the Capital Health Development Research Project,China(Grant No.2020-2-2072).
文摘Studies on pattern formation in coculture cell systems can provide insights into many physiological and pathological processes.Here,we investigate how the extracellular matrix(ECM)may influence the patterning in coculture systems.The model coculture system we use is composed of highly motile invasive breast cancer cells,initially mixed with inert nonmetastatic cells on a 2D substrate and covered with a Matrigel layer introduced to mimic ECM.We observe that the invasive cells exhibit persistent centripetal motion and yield abnormal aggregation,rather than random spreading,due to a“collective pulling”effect resulting from ECM-mediated transmission of active contractile forces generated by the polarized migration of the invasive cells along the vertical direction.The mechanism we report may open a new window for the understanding of biological processes that involve multiple types of cells.
基金supported by the National Key Research and Development Program of China(No.2020YFA0908200)the Emergency Project of Wenzhou(No.ZY202005)+2 种基金the Youth Innovation Promotion Association of CAS(No.2021007)the Engineering Research Center of Clinical Functional Materials and Diagnosis&Treatment Devices of Zhejiang Province(No.WIUCASK19006)and the Scientific Instrument Developing Project of the Chinese Academy of Sciences(No.YJKYYQ20190034).
文摘SARS-CoV-2 has caused asevere pneumoniapandemic worldwide with high morbidity and mortality.Howto developa preclinical model for recapitulating SARS-CoV-2 pathogenesis is stil urgent and essential for the control of the pandemic.Here,we have established a 3D biomimetic alveolus-on-a-chip with mechanical strain and extracellular matrix taken into consideration.We have validated that the alveolus-on-a-chip is capable of recapitulating key physiological characteristics of human alveolar units,which lays a fundamental basis for viral infection studies at the organ level.Using virus-analogous chemicals and pseudovirus,we have explored virus pathogenesis and blocking ability of antibodies during viral infection.This work provides a favorable platform for SARS-Cov-2-related researches and has a great potential for physiology and pathophysiology studies of the human lung at the organ level in vitro.
基金National Key Research and Development Program of China,Grant/Award Number:2020YFA0908200Strategic Priority Research Program of Chinese Academy of Sciences,Grant/Award Number:XDB33030300+1 种基金National Natural Science Foundation of China,Grant/Award Number:32271383Youth Innovation Promotion Association of CAS,Grant/Award Number:2021007。
文摘Adsorbents with high adsorption efficiency and excellent biosafety for biomedical applications are highly required.MXene is a promising candidate owning these advantages,yet pristine MXene faces dilemmas including insufficient utility of sur-face site as well as limited processibility.Here,we develop MXene-encapsulated porous microcapsules via microfluidics.The microcapsules have a biomass hydrogel shell that provides robust support for MXene in the core,by which the microcapsules are endowed with high MXene dosage and remarkable biosafety.Additionally,the MXene nanoflakes assemble into a three-dimensional network via metal ion-induced gelation,thereby avoiding restacking and significantly improving surface utiliza-tion.Moreover,a freeze-pretreatment of the microcapsules during preparation results in the formation of a macroporous structure in the shell,which can facilitate the diffusion of the target molecules.These features,combined with additional magneto-responsiveness rendered by the incorporation of magnetic nanoparticles,contribute to prominent performances of the microcapsules in cleaning uremia toxins including creatinine,urea,and uric acid.Thus,it is anticipated that the MXene-encapsulated microcapsules will be promising adsorbents in dialysis-related applications,and the combination of microfluidic encapsulation with metal ion gelation will provide a novel approach for construction of hybrid MXene materials with desired functions.
基金the National Key Research and Development Program of China(2020YFA0908200,2018YFA0902600,2020YFA0712102,and 2020YFA0712102)the National Natural Science Foundation of China(12074407,11774394,22125701,21834007,and 21907088)+1 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(XDB33000000)the Youth Innovation Promotion Association of CAS(2020228,2021007).
文摘Cellular collective motion in confluent epithelial monolayers is involved in many processes such as embryo development,carcinoma invasion,and wound healing.The development of new chemical strategies to achieve largescale control of cells’collective motion is essential for biomedical applications.Here a series of DNA nanostructures with different dimensions were synthesized and their influences on cells’collective migration and packing behaviors in epithelial monolayers were investigated.We found that the framed DNA nanoassemblies effectively reduced the cells’speed by increasing the rigidity of cells,while the lipid-DNA micelles had a more pronounced effect on cells’projection area and shape factor.These DNA nanostructures all significantly enhanced the dependence of cells’speed on their shape factor.Our results indicate that cells’mobility in monolayers can be manipulated by chemical intercellular interactions without any genetic intervention.This may provide a new chemical strategy for tissue engineering and tumor therapy.
基金supported by the National Key Research and Development Program of China[2020YFA0908200]the National Natural Science Foundation of China(NSFC)[Grant Nos.12074406,12074407,and 12090054]+3 种基金the Strategic Priority Research Program of Chinese Academy of Sciences[Grant No.XDB33000000]the Youth Innovation Promotion Association of CAS[No.2021007]the Postdoctoral International Exchange Program[No.2020000234]the International Young Scientist Fellowship[No.202002]of the Institute of Physics,CAS.
文摘Microglia are resident macrophage cells in the central nervous system that search for pathogens or abnormal neural activities and migrate to resolve the issues.The effective search and targeted motion of macrophages mean dearly to maintaining a healthy brain,yet little is known about their migration dynamics.In this work,we study microglial motion with and without the presence of external mechanostimuli.We discover that the cells are promptly attracted by the applied forces(i.e.,mechanotaxis),which is a tactic behavior as yet unconfirmed in microglia.Meanwhile,in both the explorative and the targeted migration,microglia display dynamics that is strikingly analogous to bacterial run-and-tumble motion.A closer examination reveals that microglial run-and-tumble is more sophisticated,e.g.,they display a short-term memory when tumbling and rely on active steering during runs to achieve mechanotaxis,probably via the responses of mechanosensitive ion channels.These differences reflect the sharp contrast between microglia and bacteria cells(eukaryotes vs.prokaryotes)and their environments(compact tissue vs.fluid).Further analyses suggest that the reported migration dynamics has an optimal search efficiency and is shared among a subset of immune cells(human monocyte and macrophage).This work reveals a fruitful analogy between the locomotion of 2 remote systems and provides a framework for studying immune cells exploring complex environments.
基金supported by the National Naturai Science Foundation of China(Grant Nos.11774394,11974066,12074407,and 12090054)the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB330000)+2 种基金the Start-Up Fund and University Graduate Fllowship of Arizona State University,the Natural Science Foundation of Chongqing Municipal Science and Technology Commission(Grant No.cstc2019jcyj-msxmX0477)the Fundamental Research Funds for the Central Universities(Grant No.2019CDYGYB007)and the Capital Health Development Research Project,China(Grant No.2020-2-2072).
文摘Studiesonpattern formation in coculturecell systemscan provide insights intomany physiological and pathologicalprocesses Here,we investigate how theextracellular matrix(ECM)may influence the patterning in coculture systems.Themodel coculture system we use is composed of highly motile invasivebreast cancer cells,initially mixed with inert nonmetastatic cells on a 2D substrate and covered with a Matrigel layer introduced to mimic ECM.We observe that the invasive cells exhibit persistent centripetal motion and yield abnormal aggregation,rather than random spreading,due to a“cllective pulling”effect resultingfrom ECM-mediated transmssion of active contractile forces generated bythe polarized migration of the invasive cells along the vertical direction.Themechanism we report may open a new window for the understanding of biological processes that involve multiple types of cells.
基金supported by the National Key Research and Develop-ment Program of China(2020YFA0908200)the National Natural Sci-ence Foundation of China(22002018)+2 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(XDB33030300)the Youth Innovation Promotion Association of CAS(2021007)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai In-stitutions of Higher Learning(SSH1340011).
文摘Adsorption or enrichment has been an indispensable and important measure in biomedical engineering since it is promising in diagnosis and treatment of complex diseases.The ongoing development in this arena starves for exploration of outstanding adsorptive materials.As an excellent candidate for adsorption or enrichment carriers,carbon-based material has demonstrated unique superiority in biomedical arena owing to its integrated charac-teristics.Herein,we review the lasted advance in adsorptive carbon-based materials for biomedical application with emphasis on carbon nanotubes(CNTs)-based,graphene-based,and biomass/polymer-based ones.We begin with the classification of different carbon-based materials and elaborate the respective preparation approaches that are utilized to realize optimized microstructure and physicochemical property.Afterwards,we introduce the different applications of carbon-based materials in biomedical arena,including blood purification,enrichment of glycopeptide and phosphopeptide,and breath analysis.Finally,we present a concise summary and give an outlook of this arena.
基金supported by the National Natural Science Foundation of China(Grant No.32101159)the WIUCAS’Startup Fund(Grant No.WIUCASQD2019007)+1 种基金the Youth Innovation Promotion Association of CAS(Grant No.2021007)the Engineering Research Center of Clin-ical Functional Materials and Diagnosis&Treatment Devices of Zhejiang Province(Grant No.WIUCASK19006).
文摘Primary liver cancer is the fifth most common malignancy and the third leading cause of cancer death worldwide.Although current advances in the treatment of liver cancer,the prognosis of this cancer remains unfavorable.Appropriate liver cancer model in vitro is an important way to study the pathogenesis and drug screening of liver cancer.This review provides a comprehensive summary and discussion on the construction and application of liver cancer models in vitro,in particular hepatocellular carcinoma(HCC).Specifically,after introducing the current methods or techniques for preparing 3D in vitro liver cancer models,this review summarizes the relevant applications of these liver cancer models in vitro,e.g.drug screening,personalized medicine,and other applications.In the end,this review discusses the advantages and disadvantages of the liver cancer models in vitro,and proposes future prospects and research directions.
