Pub Date : 2024-07-05DOI: 10.1038/s41563-024-01942-9
Eirini Maniou, Silvia Todros, Anna Urciuolo, Dale A Moulding, Michael Magnussen, Ioakeim Ampartzidis, Luca Brandolino, Pietro Bellet, Monica Giomo, Piero G Pavan, Gabriel L Galea, Nicola Elvassore
Morphogenesis requires embryonic cells to generate forces and perform mechanical work to shape their tissues. Incorrect functioning of these force fields can lead to congenital malformations. Understanding these dynamic processes requires the quantification and profiling of three-dimensional mechanics during evolving vertebrate morphogenesis. Here we describe elastic spring-like force sensors with micrometre-level resolution, fabricated by intravital three-dimensional bioprinting directly in the closing neural tubes of growing chicken embryos. Integration of calibrated sensor read-outs with computational mechanical modelling allows direct quantification of the forces and work performed by the embryonic tissues. As they displace towards the embryonic midline, the two halves of the closing neural tube reach a compression of over a hundred nano-newtons during neural fold apposition. Pharmacological inhibition of Rho-associated kinase to decrease the pro-closure force shows the existence of active anti-closure forces, which progressively widen the neural tube and must be overcome to achieve neural tube closure. Overall, our approach and findings highlight the intricate interplay between mechanical forces and tissue morphogenesis.
{"title":"Quantifying mechanical forces during vertebrate morphogenesis.","authors":"Eirini Maniou, Silvia Todros, Anna Urciuolo, Dale A Moulding, Michael Magnussen, Ioakeim Ampartzidis, Luca Brandolino, Pietro Bellet, Monica Giomo, Piero G Pavan, Gabriel L Galea, Nicola Elvassore","doi":"10.1038/s41563-024-01942-9","DOIUrl":"10.1038/s41563-024-01942-9","url":null,"abstract":"<p><p>Morphogenesis requires embryonic cells to generate forces and perform mechanical work to shape their tissues. Incorrect functioning of these force fields can lead to congenital malformations. Understanding these dynamic processes requires the quantification and profiling of three-dimensional mechanics during evolving vertebrate morphogenesis. Here we describe elastic spring-like force sensors with micrometre-level resolution, fabricated by intravital three-dimensional bioprinting directly in the closing neural tubes of growing chicken embryos. Integration of calibrated sensor read-outs with computational mechanical modelling allows direct quantification of the forces and work performed by the embryonic tissues. As they displace towards the embryonic midline, the two halves of the closing neural tube reach a compression of over a hundred nano-newtons during neural fold apposition. Pharmacological inhibition of Rho-associated kinase to decrease the pro-closure force shows the existence of active anti-closure forces, which progressively widen the neural tube and must be overcome to achieve neural tube closure. Overall, our approach and findings highlight the intricate interplay between mechanical forces and tissue morphogenesis.</p>","PeriodicalId":19058,"journal":{"name":"Nature Materials","volume":null,"pages":null},"PeriodicalIF":37.2,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1038/s41563-024-01949-2
The generation of attosecond pulses has opened the door to probing electron dynamics at sub-atomic scales. Beyond atomic physics, this field is envisioned to also have a decisive impact on condensed-matter physics, chemistry and biology.
{"title":"Into the attosecond era","authors":"","doi":"10.1038/s41563-024-01949-2","DOIUrl":"10.1038/s41563-024-01949-2","url":null,"abstract":"The generation of attosecond pulses has opened the door to probing electron dynamics at sub-atomic scales. Beyond atomic physics, this field is envisioned to also have a decisive impact on condensed-matter physics, chemistry and biology.","PeriodicalId":19058,"journal":{"name":"Nature Materials","volume":null,"pages":null},"PeriodicalIF":37.2,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41563-024-01949-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1038/s41563-024-01908-x
Bauer L. LeSavage, Daiyao Zhang, Carla Huerta-López, Aidan E. Gilchrist, Brad A. Krajina, Kasper Karlsson, Amber R. Smith, Kremena Karagyozova, Katarina C. Klett, Michelle S. Huang, Christopher Long, Gernot Kaber, Christopher M. Madl, Paul L. Bollyky, Christina Curtis, Calvin J. Kuo, Sarah C. Heilshorn
Pancreatic ductal adenocarcinoma (PDAC) is characterized by its fibrotic and stiff extracellular matrix. However, how the altered cell/extracellular-matrix signalling contributes to the PDAC tumour phenotype has been difficult to dissect. Here we design and engineer matrices that recapitulate the key hallmarks of the PDAC tumour extracellular matrix to address this knowledge gap. We show that patient-derived PDAC organoids from three patients develop resistance to several clinically relevant chemotherapies when cultured within high-stiffness matrices mechanically matched to in vivo tumours. Using genetic barcoding, we find that while matrix-specific clonal selection occurs, cellular heterogeneity is not the main driver of chemoresistance. Instead, matrix-induced chemoresistance occurs within a stiff environment due to the increased expression of drug efflux transporters mediated by CD44 receptor interactions with hyaluronan. Moreover, PDAC chemoresistance is reversible following transfer from high- to low-stiffness matrices, suggesting that targeting the fibrotic extracellular matrix may sensitize chemoresistant tumours. Overall, our findings support the potential of engineered matrices and patient-derived organoids for elucidating extracellular matrix contributions to human disease pathophysiology. Patient-derived pancreatic cancer organoids grown in engineered matrices acquire chemoresistance due to the increased expression of drug efflux transporters, promoted by CD44 receptor interactions with hyaluronan in the stiffer tumoural matrix.
{"title":"Engineered matrices reveal stiffness-mediated chemoresistance in patient-derived pancreatic cancer organoids","authors":"Bauer L. LeSavage, Daiyao Zhang, Carla Huerta-López, Aidan E. Gilchrist, Brad A. Krajina, Kasper Karlsson, Amber R. Smith, Kremena Karagyozova, Katarina C. Klett, Michelle S. Huang, Christopher Long, Gernot Kaber, Christopher M. Madl, Paul L. Bollyky, Christina Curtis, Calvin J. Kuo, Sarah C. Heilshorn","doi":"10.1038/s41563-024-01908-x","DOIUrl":"10.1038/s41563-024-01908-x","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is characterized by its fibrotic and stiff extracellular matrix. However, how the altered cell/extracellular-matrix signalling contributes to the PDAC tumour phenotype has been difficult to dissect. Here we design and engineer matrices that recapitulate the key hallmarks of the PDAC tumour extracellular matrix to address this knowledge gap. We show that patient-derived PDAC organoids from three patients develop resistance to several clinically relevant chemotherapies when cultured within high-stiffness matrices mechanically matched to in vivo tumours. Using genetic barcoding, we find that while matrix-specific clonal selection occurs, cellular heterogeneity is not the main driver of chemoresistance. Instead, matrix-induced chemoresistance occurs within a stiff environment due to the increased expression of drug efflux transporters mediated by CD44 receptor interactions with hyaluronan. Moreover, PDAC chemoresistance is reversible following transfer from high- to low-stiffness matrices, suggesting that targeting the fibrotic extracellular matrix may sensitize chemoresistant tumours. Overall, our findings support the potential of engineered matrices and patient-derived organoids for elucidating extracellular matrix contributions to human disease pathophysiology. Patient-derived pancreatic cancer organoids grown in engineered matrices acquire chemoresistance due to the increased expression of drug efflux transporters, promoted by CD44 receptor interactions with hyaluronan in the stiffer tumoural matrix.","PeriodicalId":19058,"journal":{"name":"Nature Materials","volume":null,"pages":null},"PeriodicalIF":37.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1038/s41563-024-01936-7
Marcus E. Peter, Maartje M. C. Bastings
A pH-activatable DNA origami nanostructure with geometrically patterned CD95 ligands reverses symptoms in a mouse model of rheumatoid arthritis without apparent side effects.
具有几何图案 CD95 配体的 pH 可激活 DNA 折纸纳米结构可逆转类风湿性关节炎小鼠模型的症状，且无明显副作用。
{"title":"Unfolding a death signal to treat rheumatoid arthritis","authors":"Marcus E. Peter, Maartje M. C. Bastings","doi":"10.1038/s41563-024-01936-7","DOIUrl":"10.1038/s41563-024-01936-7","url":null,"abstract":"A pH-activatable DNA origami nanostructure with geometrically patterned CD95 ligands reverses symptoms in a mouse model of rheumatoid arthritis without apparent side effects.","PeriodicalId":19058,"journal":{"name":"Nature Materials","volume":null,"pages":null},"PeriodicalIF":37.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1038/s41563-024-01912-1
Mengwei He, William J. Davids, Andrew J. Breen, Simon P. Ringer
Medium- and high-entropy alloys are an emerging class of materials that can exhibit outstanding combinations of strength and ductility for engineering applications. Computational simulations have suggested the presence of short-range order (SRO) in these alloys, and recent experimental evidence is also beginning to emerge. Unfortunately, the difficulty in quantifying the SRO under different heat treatment conditions has generated much debate on the atomic preferencing and implications of SRO on mechanical properties. Here we develop an approach to measure SRO using atom probe tomography. This method balances the limitations of atom probe tomography with the threshold values of SRO to map the regimes where the required atomistic neighbourhood information is preserved and where it is not. We demonstrate the method with a case study of the CoCrNi alloy and use this to monitor SRO changes induced by heat treatments. These species-specific SRO measurements enable the generation of computational simulations of atomic neighbourhood models that are equivalent to the experiment and can contribute to the further understanding and design of medium- and high-entropy alloys and other materials systems where SRO may occur. A method is introduced to quantify short-range order in multicomponent alloys using atom probe tomography, which enables further understanding and materials design related to atomic-scale solute engineering.
{"title":"Quantifying short-range order using atom probe tomography","authors":"Mengwei He, William J. Davids, Andrew J. Breen, Simon P. Ringer","doi":"10.1038/s41563-024-01912-1","DOIUrl":"10.1038/s41563-024-01912-1","url":null,"abstract":"Medium- and high-entropy alloys are an emerging class of materials that can exhibit outstanding combinations of strength and ductility for engineering applications. Computational simulations have suggested the presence of short-range order (SRO) in these alloys, and recent experimental evidence is also beginning to emerge. Unfortunately, the difficulty in quantifying the SRO under different heat treatment conditions has generated much debate on the atomic preferencing and implications of SRO on mechanical properties. Here we develop an approach to measure SRO using atom probe tomography. This method balances the limitations of atom probe tomography with the threshold values of SRO to map the regimes where the required atomistic neighbourhood information is preserved and where it is not. We demonstrate the method with a case study of the CoCrNi alloy and use this to monitor SRO changes induced by heat treatments. These species-specific SRO measurements enable the generation of computational simulations of atomic neighbourhood models that are equivalent to the experiment and can contribute to the further understanding and design of medium- and high-entropy alloys and other materials systems where SRO may occur. A method is introduced to quantify short-range order in multicomponent alloys using atom probe tomography, which enables further understanding and materials design related to atomic-scale solute engineering.","PeriodicalId":19058,"journal":{"name":"Nature Materials","volume":null,"pages":null},"PeriodicalIF":37.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41563-024-01912-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1038/s41563-024-01920-1
Jan-Chi Yang, Ying-Hao Chu
The synergy between the field-induced antiferroelectric to ferroelectric phase transition and substrate constraints results in enhanced electromechanical responses.
场诱导的反铁电到铁电相变与衬底约束之间的协同作用增强了机电响应。
{"title":"Boosting electromechanical response via clamping","authors":"Jan-Chi Yang, Ying-Hao Chu","doi":"10.1038/s41563-024-01920-1","DOIUrl":"10.1038/s41563-024-01920-1","url":null,"abstract":"The synergy between the field-induced antiferroelectric to ferroelectric phase transition and substrate constraints results in enhanced electromechanical responses.","PeriodicalId":19058,"journal":{"name":"Nature Materials","volume":null,"pages":null},"PeriodicalIF":37.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1038/s41563-024-01923-y
Masahito Mochizuki
Researchers have demonstrated that skyrmion-like topological spin textures can be created in a controlled manner via the local application of an electric field with a tip electrode on a multiferroic BiFeO3 thin film.
{"title":"Writing a magnetic whirl on multiferroics","authors":"Masahito Mochizuki","doi":"10.1038/s41563-024-01923-y","DOIUrl":"10.1038/s41563-024-01923-y","url":null,"abstract":"Researchers have demonstrated that skyrmion-like topological spin textures can be created in a controlled manner via the local application of an electric field with a tip electrode on a multiferroic BiFeO3 thin film.","PeriodicalId":19058,"journal":{"name":"Nature Materials","volume":null,"pages":null},"PeriodicalIF":37.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1038/s41563-024-01932-x
José Capmany, Daniel Pérez-López
Harnessing the large-scale integration and individual control of artificial atoms on silicon photonic circuits enables the realization of a rapidly programmable topological photonic chip that can be dynamically reconfigured to explore diverse topological phenomena.
{"title":"Programming topological photonics","authors":"José Capmany, Daniel Pérez-López","doi":"10.1038/s41563-024-01932-x","DOIUrl":"10.1038/s41563-024-01932-x","url":null,"abstract":"Harnessing the large-scale integration and individual control of artificial atoms on silicon photonic circuits enables the realization of a rapidly programmable topological photonic chip that can be dynamically reconfigured to explore diverse topological phenomena.","PeriodicalId":19058,"journal":{"name":"Nature Materials","volume":null,"pages":null},"PeriodicalIF":37.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1038/s41563-024-01929-6
Zhiping Xu, Zian Zhang
{"title":"The need for standardizing fatigue data reporting","authors":"Zhiping Xu, Zian Zhang","doi":"10.1038/s41563-024-01929-6","DOIUrl":"10.1038/s41563-024-01929-6","url":null,"abstract":"","PeriodicalId":19058,"journal":{"name":"Nature Materials","volume":null,"pages":null},"PeriodicalIF":37.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1038/s41563-024-01934-9
Roy van der Meel, Francesca Grisoni, Willem J. M. Mulder
Combining machine learning with high-throughput synthesis expedites ionizable cationic lipid development for nanoparticle-based messenger RNA delivery.
将机器学习与高通量合成相结合，加快可离子化阳离子脂质的开发，用于基于纳米粒子的信使 RNA 递送。
{"title":"Lipid discovery for mRNA delivery guided by machine learning","authors":"Roy van der Meel, Francesca Grisoni, Willem J. M. Mulder","doi":"10.1038/s41563-024-01934-9","DOIUrl":"10.1038/s41563-024-01934-9","url":null,"abstract":"Combining machine learning with high-throughput synthesis expedites ionizable cationic lipid development for nanoparticle-based messenger RNA delivery.","PeriodicalId":19058,"journal":{"name":"Nature Materials","volume":null,"pages":null},"PeriodicalIF":37.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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