SCIENTIFIC PUBLICATIONS
supporting 4Dcell technologies
Explore peer-reviewed research and published scientific studies involving 4Dcell technologies for human 3D cardiac microtissues, cell micropatterning, mechanobiology and advanced in vitro models.
These publications document the use of engineered cell culture platforms to investigate tissue function, cellular organization, disease mechanisms and pharmacological responses.
HUMAN 3D CARDIAC MODELS - SMARTHEART®
SmartHeart® is 4Dcell's human 3D cardiac microtissue platform for studying cardiac contractility, drug responses and disease-related functional phenotypes.
The following scientific publications document the development of ring-shaped cardiac tissues, their pharmacological characterization and their application to human cardiac disease modeling.
A versatile high-throughput assay based on 3D ring-shaped cardiac tissues generated from human induced pluripotent stem cell-derived cardiomyocytes
Séguret M. et al. | eLife | 2024 | DOI: 10.7554/eLife.87739
This study describes the development of a 96-well platform for generating self-assembled, ring-shaped human cardiac microtissues around optically transparent, deformable hydrogel pillars.
The tissues were generated from human iPSC-derived cardiomyocytes and adult human dermal fibroblasts. The study demonstrated reproducible tissue formation, quantitative assessment of cardiac mechanical activity and pharmacological responses to isoproterenol, verapamil and dofetilide.
The results establish the scientific foundation of SmartHeart's ring-shaped cardiac tissue architecture and its use for investigating drug-induced changes in cardiac function.
Experimental configuration: human iPSC-derived cardiomyocytes and adult human dermal fibroblasts (3:1 ratio). The cell composition and experimental conditions differ from those used in 4Dcell's current qualified contractility testing workflow.
LMNA p.H222P mutation causes contractile dysfunction via impaired mitochondrial calcium uptake in human cardiac laminopathy
Séguret M. et al. | Cardiovascular Research | 2026 | DOI: 10.1093/cvr/cvag163
This independent academic study used 4Dcell's SmartHeart® ring-shaped cardiac tissue platform to investigate functional abnormalities associated with the LMNA p.H222P mutation in human iPSC-derived cardiomyocytes.
Compared with isogenic corrected controls, LMNA-mutant cardiac tissues exhibited impaired contractile function. Complementary analyses identified alterations in mitochondrial calcium uptake, mitochondrial respiration and cellular energy metabolism.
Treatment with the mitochondrial calcium uniporter activator amorolfine improved calcium uptake and cardiac contractility.
This study illustrates how human 3D cardiac microtissues can contribute to disease-mechanism investigations and the assessment of pharmacological rescue in inherited cardiomyopathy.
PUBLISHED SCIENTIFIC ABSTRACTS
SmartHeart: An innovative high throughput assay to generate and assess cardiac micro tissues from hiPSCs answering to the current challenges of drug discovery
Khedher A. et al. | Journal of Pharmacological and Toxicological Methods | 2025 | Published abstract | DOI: 10.1016/j.vascn.2025.107821
This published abstract presents the SmartHeart® platform as a human 3D cardiac microtissue model combining quantitative contractility measurements with complementary optical functional readouts.
The study reports pharmacological responses to isoproterenol, nifedipine and mexiletine, illustrating the use of ring-shaped cardiac tissues to investigate positive and negative inotropic effects and changes in beating activity.
It also describes the platform's compatibility with fluorescence-based measurements of cardiac electrical activity and tissue organization.
CELL MICROPATTERNING & MECHANOBIOLOGY - SMARTPATTERN®
SmartPattern® technologies enable researchers to control cell adhesion geometry and spatial organization, supporting reproducible experimental conditions for studying cell morphology, mechanotransduction and cellular responses to physical cues.
The scientific literature associated with SmartPattern applications covers cell–substrate interactions, nuclear mechanics, sarcomere organization, cytoskeletal dynamics and cell migration.
Explore selected research studies and discover how micropatterned culture systems contribute to controlled in vitro experimentation.
A switchable light-responsive azopolymer conjugating protein micropatterns with topography for mechanobiological studies
Chiara Cimmino, Paolo A. Netti, Maurizio Ventre | Frontiers in Bioengineering and Biotechnology | 2022
This study investigates dynamic control of cell adhesion and morphology using light-responsive azopolymer substrates combined with protein micropatterning.
The approach enables controlled modifications of substrate topography and cell adhesion, allowing researchers to investigate focal adhesion remodeling, cytoskeletal reorganization and changes in nuclear morphology.
A role for nuclear stretching and NPCs changes in the cytoplasmic-nuclear trafficking of YAP: An experimental and numerical modelling approach
Stefania Saporito, Carlo F. Natale, Costantino Menna, Paolo Antonio Netti, Maurizio Ventre | Materials Today Bio | 2022
This study combines experimental measurements and numerical modeling to investigate how nuclear deformation and nuclear pore complex changes influence YAP transport between the cytoplasm and the nucleus.
The findings contribute to understanding how mechanical forces and cellular geometry regulate mechanotransduction and intracellular signaling.
Monitoring the maturation of the sarcomere network: a super-resolution microscopy-based approach
Anna Skorska, Lisa Johann, Oleksandra Chabanovska, Praveen Vasudevan, Sophie Kussauer, Maximilian Hillemanns, Markus Wolfien, Anika Jonitz-Heincke, Olaf Wolkenhauer, Rainer Bader, Hermann Lang, Robert David, Heiko Lemcke | Cellular and Molecular Life Sciences | 2022
This study presents a super-resolution microscopy approach to investigate the structural organization and maturation of sarcomeres in cardiac cells.
The work contributes to quantitative characterization of contractile structures and the assessment of cardiac cell maturation in vitro.
ERRα coordinates actin and focal adhesion dynamics
Violaine Tribollet, Catherine Cerutti, Alain Géloën, Emmanuelle Berger, Richard De Mets, Martial Balland, Julien Courchet, Jean-Marc Vanacker, Christelle Forcet | Cancer Gene Therapy | 2022
This study investigates the role of estrogen-related receptor alpha (ERRα) in coordinating actin cytoskeleton organization and focal adhesion dynamics.
The findings provide insights into the cellular mechanisms controlling adhesion, morphology and migration, processes relevant to mechanobiology and cancer cell behavior.
Lamin mutations cause increased YAP nuclear entry in muscle stem cells
Daniel J. Owens, Martina Fischer, Saline Jabre, Sophie Moog, Kamel Mamchaoui, Gillian Butler-Browne, Catherine Coirault | Cells | 2020
This study investigates how mutations affecting nuclear lamins alter mechanosensitive signaling in muscle stem cells.
The results demonstrate increased nuclear localization of YAP in cells carrying lamin mutations, highlighting connections between nuclear structure, mechanotransduction and muscle cell biology.
Compliant substrates enhance macrophage cytokine release and NLRP3 inflammasome formation during their pro-inflammatory response
Joan-Carles Escolano, Anna V. Taubenberger, Shada Abuhattum, Christine Schweitzer, Aleeza Farrukh, Aránzazu del Campo, Clare E. Bryant, Jochen Guck | Frontiers in Cell and Developmental Biology | 2021
This study investigates how substrate stiffness influences macrophage inflammatory responses.
The authors show that compliant substrates can enhance NLRP3 inflammasome formation and the release of pro-inflammatory cytokines. Cell micropatterning experiments help distinguish the effects of cell spreading from those of substrate stiffness.
These results highlight the importance of physical microenvironment properties in immune-cell function.
Reprogramming progressive cells display low CAG promoter activity
Xiao Hu, Qiao Wu, Jian Zhang, Jonghun Kim, Xinyue Chen, Amaleah A. Hartman, Anna E. Eastman, In-Hyun Park, Shangqin Guo | STEM CELLS | 2021
This study investigates cellular heterogeneity during somatic cell reprogramming toward pluripotency.
The researchers identify low CAG promoter activity as a characteristic associated with cells progressing efficiently through reprogramming, providing insights into the relationship between cell state, proliferation and reprogramming potential.
CELL CONFINEMENT & NUCLEAR MECHANICS - SMARTCONFINER®
SmartConfiner® technologies enable researchers to investigate cellular responses to controlled physical confinement.
Published studies associated with these approaches explore nuclear deformation, cellular mechanosensing, cell-cycle regulation, nuclear envelope integrity and adaptation to spatial constraints.
Nuclear tension controls mitotic entry by regulating cyclin B1 nuclear translocation
Margarida Dantas, Andreia Oliveira, Paulo Aguiar, Helder Maiato, Jorge G. Ferreira | Journal of Cell Biology | 2022
This study investigates how mechanical tension acting on the nucleus regulates the timing of mitotic entry.
The authors demonstrate that nuclear tension influences cyclin B1 nuclear translocation, revealing a connection between mechanical forces, nuclear organization and cell-cycle progression.
The nucleus measures shape changes for cellular proprioception to control dynamic cell behavior
Valeria Venturini, Fabio Pezzano, Frederic Català Castro, Hanna-Maria Häkkinen, Senda Jiménez-Delgado, Mariona Colomer-Rosell, Monica Marro, Queralt Tolosa-Ramon, Sonia Paz-López, Miguel A. Valverde, Julian Weghuber, Pablo Loza-Alvarez, Michael Krieg, Stefan Wieser, Verena Ruprecht | Science | 2020
This study demonstrates that the cell nucleus acts as a mechanical sensor of changes in cell shape.
The findings reveal how nuclear deformation contributes to cellular responses to physical confinement and helps regulate dynamic cell behavior and migration.
The research highlights the role of nuclear mechanics in the adaptation of cells to their physical microenvironment.
A flagellate-to-amoeboid switch in the closest living relatives of animals
Thibaut Brunet, Marvin Albert, William Roman, Maxwell C. Coyle, Danielle C. Spitzer, Nicole King | eLife | 2021
This study investigates how physical confinement triggers a transition from flagellated to amoeboid cell morphology in choanoflagellates, the closest living relatives of animals.
The results demonstrate that mechanical confinement can induce changes in cellular organization and activate myosin-dependent motility, providing insights into the evolutionary origins of amoeboid cell behavior.
Mechanisms of A-type lamin targeting to nuclear ruptures are disrupted in LMNA- and BANF1-associated progerias
Rhiannon M. Sears, Kyle J. Roux | Cells | 2022
This study investigates the mechanisms responsible for recruiting A-type lamins to sites of nuclear envelope rupture.
The authors show how mutations associated with premature aging syndromes disrupt lamin recruitment and nuclear envelope repair, providing insights into nuclear integrity and the consequences of altered nuclear mechanics.
CELL MIGRATION & CONTROLLED MICROENVIRONMENTS - SMARTCHANNEL®
SmartChannel® technologies support the investigation of cell migration and cellular behavior within controlled microenvironments.
The associated scientific literature covers immune-cell trafficking, migration through confined spaces, nuclear deformation, cancer-cell invasion and cellular interactions with tissue microenvironments.
These studies highlight the importance of physical constraints, cytoskeletal organization and cell–environment interactions in regulating cellular migration.
Slow integrin-dependent migration organizes networks of tissue-resident mast cells
Lukas Kaltenbach, Paloma Martzloff, Sarah K. Bambach, et al. | Nature Immunology | 2023
This study investigates how integrin-dependent migration contributes to the spatial organization of tissue-resident mast cells.
The findings demonstrate that slow cellular migration plays a role in establishing and maintaining mast-cell networks within tissues, providing insights into immune-cell organization and tissue surveillance.
Nuclear segmentation facilitates neutrophil migration
Connie Shen, Eva Mulder, Wiebe Buitenwerf, Jérémy Postat, Aron Jansen, Matthijs Kox, Judith N. Mandl, Nienke Vrisekoop | Journal of Cell Science | 2023
This study investigates the contribution of nuclear segmentation to neutrophil migration.
The results provide insights into how the distinctive nuclear morphology of neutrophils facilitates their movement through restrictive environments, highlighting the relationship between nuclear architecture and immune-cell motility.
Specification of CNS macrophage subsets occurs postnatally in defined niches
Takahiro Masuda, Lukas Amann, Gianni Monaco, Roman Sankowski, et al. | Nature | 2022
This study investigates the developmental origin and specialization of macrophage populations within the central nervous system.
The findings demonstrate that distinct macrophage subsets emerge through specific developmental processes and interactions with defined tissue niches.
The research provides insights into immune-cell organization and the importance of local microenvironments in shaping cellular identity.
Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion
Sylvie Deborde, Laxmi Gusain, Ann Powers, Andrea Marcadis, Yasong Yu, Chun-Hao Chen, et al. | Cancer Discovery | 2022
This study demonstrates how Schwann cells can undergo reprogramming in the pancreatic tumor microenvironment and organize into dynamic cellular tracks.
These structures promote cancer-cell migration and invasion, revealing a mechanism through which interactions between tumor cells and surrounding stromal cells contribute to cancer progression.
The findings highlight the role of cellular organization and microenvironmental interactions in tumor invasion.
Snail augments nuclear deformability to promote lymph node metastasis of head and neck squamous cell carcinoma
Yin-Quan Chen, Chen-Yu Hung, Ming-Tzo Wei, Jean-Cheng Kuo, Muh-Hwa Yang, Han-Ying Cheng, Arthur Chiou | Frontiers in Cell and Developmental Biology | 2022
This study investigates how the transcription factor Snail influences nuclear deformability and the metastatic behavior of head and neck squamous cell carcinoma cells.
The findings link changes in nuclear mechanical properties to the ability of cancer cells to migrate through restrictive environments and contribute to lymph node metastasis.
Formin-like 1 mediates effector T cell trafficking to inflammatory sites to enable T cell-mediated autoimmunity
Scott B. Thompson, Adam M. Sandor, Victor Lui, Jeffrey W. Chung, Monique M. Waldman, Robert A. Long, Miriam L. Estin, Jennifer L. Matsuda, Rachel S. Friedman, Jordan Jacobelli | eLife | 2020
This study investigates the role of Formin-like 1 (FMNL1) in regulating effector T-cell migration through restrictive tissue environments.
The results show that FMNL1-dependent actin polymerization supports the passage of the nucleus through physical barriers and contributes to T-cell trafficking into inflamed tissues.
The findings identify a cytoskeletal mechanism associated with immune-cell migration and autoimmune responses.
Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton
Katharina Vestre, Irene Persiconi, Marita Borg Distefano, Nadia Mensali, Noemi Antonella Guadagno, Marine Bretou, Sébastien Wälchli, Catharina Arnold-Schrauf, Oddmund Bakke, Marc Dalod, Ana-Maria Lennon-Dumenil, Cinzia Progida | Journal of Cell Science | 2021
This study investigates how the small GTPase Rab7b contributes to dendritic cell migration.
The authors identify a functional connection between lysosomal organization and the actomyosin cytoskeleton, revealing how intracellular trafficking and cytoskeletal dynamics cooperate to regulate immune-cell motility.
A Dock8-dependent mechanosensitive central actin pool maintains T cell shape and protects the nucleus during migration
Connie Shen, Aysha Cerf, Jérémy Postat, Aanya Bhagrath, Mauricio Merino, Angela Mingarelli, Grace Barnes, Dhanesh Patel, Dakota Rogers, Vincent M. Luo, et al. | Science Immunology | 2025
This study identifies a mechanosensitive central actin structure that helps T cells maintain their shape and protect their nuclei during migration through confined environments.
The authors demonstrate that Dock8 contributes to the formation of this actin structure. Its disruption increases nuclear deformation and DNA damage, highlighting the importance of cytoskeletal organization in immune-cell migration and survival.
ENGINEERED BIOMATERIALS & CARDIAC CELL ORGANIZATION - SMARTGEL®
SmartGel® technology is associated with research involving engineered cell culture environments and the regulation of cell behavior through physical and intercellular interactions.
The following publication investigates mechanisms involved in the structural and functional organization of cardiac pacemaker cells.
Adherens junction engagement regulates functional patterning of the cardiac pacemaker cell lineage
Kandace Thomas, Trevor Henley, Simone Rossi, M. Joseph Costello, William Polacheck, Boyce E. Griffith, Michael Bressan | Developmental Cell | 2021
This study investigates how adherens junction engagement influences the structural and functional organization of cardiac pacemaker cells.
The authors show that changes in cell–cell adhesion contribute to the regulation of cell morphology, gap junction organization and electrical excitability.
These findings provide insights into how cellular architecture and mechanical interactions influence the development and function of cardiac pacemaker cells.
FROM SCIENTIFIC RESEARCH TO HUMAN RELEVANT
IN VITRO MODELS
4Dcell combines biomaterials engineering, cell biology and quantitative analysis to develop human in vitro platforms for biomedical research and preclinical drug discovery.
Our technologies support researchers investigating cellular mechanisms, human tissue function, drug responses and disease-associated phenotypes.
Explore our experimental platforms or contact our scientific team to discuss a research question or a customized study.