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312 results on '"Kouwer, Paul H. J."'

2. The living interface between synthetic biology and biomaterial design

Author

Liu, Allen P., Appel, Eric A., Ashby, Paul D., Baker, Brendon M., Franco, Elisa, Gu, Luo, Haynes, Karmella, Joshi, Neel S., Kloxin, April M., Kouwer, Paul H. J., Mittal, Jeetain, Morsut, Leonardo, Noireaux, Vincent, Parekh, Sapun, Schulman, Rebecca, Tang, Sindy K. Y., Valentine, Megan T., Vega, Sebastián L., Weber, Wilfried, Stephanopoulos, Nicholas, and Chaudhuri, Ovijit

Published
2022
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6. Semi‐Flexible Immunobrushes Facilitate Effective and Selective Expansion of Antigen‐Specific T Cells.

Author

Gerrits, Lotte, Weiss, Lea, Grad, Emilia M., Schluck, Marjolein, Maassen, Lisa, Classens, René, Archidi, Chadia, Verdoes, Martijn, Figdor, Carl G., Kouwer, Paul H. J., and Hammink, Roel

Subjects
T cells, T cell receptors, MAJOR histocompatibility complex
Abstract

Adoptive T cell therapy (ACT) has achieved remarkable results in the treatment of cancer. Tumor‐antigen specific T cells are the main players in the clearance of cancerous cells, but generating large numbers is a major hurdle in clinical practice. One shortcoming of current expansion procedures is that the artificial presentation of T cell activating signals on rigid surfaces do not recapitulate the physiological presentation on a fluidic membrane. To address this, semi‐flexible poly(isocyanopeptide) (PIC) immunofilaments (IFs) are generated coated on micro‐sized magnetic beads (immunobrushes (IB)). IBs are functionalized with peptide‐loaded major histocompatibility complexes (pMHC, signal 1) and agonistic anti‐CD28 antibodies (αCD28, signal 2) to effectively expand and enrich antigen‐specific T cells. As a direct result of the immunobrush design, strong T cell activation and excellent tumor cell killing capacities are found. More importantly, high selectivity is demonstrated by strong expansion and enrichment of antigen‐specific T cells in a pool of non‐specific cells (93‐fold enrichment of antigen specific T cells in 7 days). The modular character of the immunobrush‐based strategy makes it a great platform for highly effective ACT‐based therapies. [ABSTRACT FROM AUTHOR]

Published
2024
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11. TempEasy3D Hydrogel Coculture System Provides Mechanistic Insights into Prostate Cancer Bone Metastasis

Author

Zhang, Zhaobao, Chen, Wen, Sun, Mingchen, Aalders, Tilly, Verhaegh, Gerald W., and Kouwer, Paul H. J.

Abstract

Patients diagnosed with advanced prostate cancer (PCa) often experience incurable bone metastases; however, a lack of relevant experimental models has hampered the study of disease mechanisms and the development of therapeutic strategies. In this study, we employed the recently established Temperature-based Easy-separable (TempEasy) 3D cell coculture system to investigate PCa bone metastasis. Through coculturing PCa and bone cells for 7 days, our results showed a reduction in PCa cell proliferation, an increase in neovascularization, and an enhanced metastasis potential when cocultured with bone cells. Additionally, we observed increased cell proliferation, higher stemness, and decreased bone matrix protein expression in bone cells when cocultured with PCa cells. Furthermore, we demonstrated that the stiffness of the extracellular matrix had a negligible impact on molecular responses in both primary (PCa cells) and distant malignant (bone cells) sites. The TempEasy3D hydrogel coculture system is an easy-to-use and versatile coculture system that provides valuable insights into the mechanisms of cell–cell communication and interaction in cancer metastasis.

Published
2024
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14. Synthetic fibrous hydrogels as a platform to decipher cell–matrix mechanical interactions

Author

Yuan, Hongbo, primary, Liu, Kaizheng, additional, Cóndor, Mar, additional, Barrasa-Fano, Jorge, additional, Louis, Boris, additional, Vandaele, Johannes, additional, de Almeida, Paula, additional, Coucke, Quinten, additional, Chen, Wen, additional, Oosterwijk, Egbert, additional, Xing, Chengfen, additional, Van Oosterwyck, Hans, additional, Kouwer, Paul H. J., additional, and Rocha, Susana, additional

Published
2023
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17. Synthetic fibrous hydrogels as a platform to decipher cell-matrix mechanical interactions

Author

Yuan, Hongbo, primary, Liu, Kaizheng, additional, Cóndor, Mar, additional, Barrasa-Fano, Jorge, additional, Louis, Boris, additional, Vandaele, Johannes, additional, de Almeida, Paula, additional, Coucke, Quinten, additional, Chen, Wen, additional, Oosterwijk, Egbert, additional, Xing, Chenfen, additional, Van Oosterwyck, Hans, additional, Kouwer, Paul H. J., additional, and Rocha, Susana, additional

Published
2022
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19. Synthetic fibrous hydrogels as a platform to decipher cell-matrix mechanical interactions.

Author

Hongbo Yuan, Kaizheng Liu, Cóndor, Mar, Barrasa-Fano, Jorge, Louis, Boris, Vandaele, Johannes, de Almeida, Paula, Coucke, Quinten, Wen Chen, Oosterwijk, Egbert, Chengfen Xing, Van Oosterwyck, Hans, Kouwer, Paul H. J., and Rocha, Susana

Subjects
NONLINEAR mechanics, MECHANICAL behavior of materials, HYDROGELS, PLANT fibers, EXTRACELLULAR matrix, CELL physiology
Abstract

Cells continuously sense external forces from their microenvironment, the extracellular matrix (ECM). In turn, they generate contractile forces, which stiffen and remodel this matrix. Although this bidirectional mechanical exchange is crucial for many cell functions, it remains poorly understood. Key challenges are that the majority of available matrices for such studies, either natural or synthetic, are difficult to control or lack biological relevance. Here, we use a synthetic, yet highly biomimetic hydrogel based on polyisocyanide (PIC) polymers to investigate the effects of the fibrous architecture and the nonlinear mechanics on cell-matrix interactions. Live-cell rheology was combined with advanced microscopy-based approaches to understand the mechanisms behind cell-induced matrix stiffening and plastic remodeling. We demonstrate how cell-mediated fiber remodeling and the propagation of fiber displacements are modulated by adjusting the biological and mechanical properties of this material. Moreover, we validate the biological relevance of our results by demonstrating that cellular tractions in PIC gels develop analogously to those in the natural ECM. This study highlights the potential of PIC gels to disentangle complex bidirectional cell-matrix interactions and to improve the design of materials for mechanobiology studies. [ABSTRACT FROM AUTHOR]

Published
2023
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25. Chromophoric Polyisocyanide Materials

Author

Keereweer, Bram, primary, Schwartz, Erik, additional, Le Gac, Stéphane, additional, Nolte, Roeland J.M., additional, Kouwer, Paul H. J., additional, and Rowan, Alan E., additional

Published
2014
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29. Synthetic Extracellular Matrices as a Toolbox to Tune Stem CellSecretome

Author

Liu, Kaizheng, Veenendaal, Tomas, Wiendels, Maury, Ruiz-Zapata, Alejandra M, van Laar, Justin, Kyranas, Rafail, Enting, Hilde, van Cranenbroek, Bram, Koenen, Hans J P M, Mihaila, Silvia M, Oosterwijk, Egbert, Kouwer, Paul H J, Afd Pharmacology, Pharmacology, Afd Pharmacology, and Pharmacology

Subjects
0301 basic medicine, Materials science, Polymers, Systems Chemistry, Cell Culture Techniques, wound healing, 02 engineering and technology, 03 medical and health sciences, Paracrine signalling, Matrix manipulation, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], Conditioned medium, Extracellular, Humans, General Materials Science, Cell Proliferation, Molecular Materials, synthetic extracellular matrices (ECM), stem cell secretome, Hydrogels, Mesenchymal Stem Cells, Fibroblasts, 021001 nanoscience & nanotechnology, Culture Media, Interleukin-10, Cell biology, interleukin-10 (IL-10), Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], 030104 developmental biology, Self-healing hydrogels, Wound closure, Stem cell, 0210 nano-technology, Wound healing, Oligopeptides, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Research Article, polyisocyanide hydrogels
Abstract

The application of stem cell-derived secretome in regenerative therapies offers the key advantage that instead of the stem cells, only their effective paracrine compounds are in vivo delivered. Ideally, the secretome can be steered by the culture conditions of the stem cells. So far, most studies use stem cells cultured on stiff plastic substrates, not representative of their native 3D environment. In this study, cells are cultured inside synthetic polyisocyanide (PIC)-based hydrogels, which are minimal, tailorable, and highly reproducible biomimetic matrices. Secretome analysis of human adipose-derived stem cells (multiplex, ELISA) displays that matrix manipulation is a powerful tool to direct the secretome composition. As an example, cells in nonadherent PIC gels secrete increased levels of IL-10 and the conditioned media from 3D culture accelerate wound closure. In all, our PIC-based approach opens the door to dedicated matrix design to engineer the secretome for custom applications.

Published
2020
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30. Synthetic Extracellular Matrices as a Toolbox to Tune Stem Cell Secretome

Author

Liu, Kaizheng, Veenendaal, Tomas, Wiendels, Maury, Ruiz-Zapata, Alejandra M, van Laar, Justin, Kyranas, Rafail, Enting, Hilde, van Cranenbroek, Bram, Koenen, Hans J P M, Mihaila, Silvia M, Oosterwijk, Egbert, Kouwer, Paul H J, Liu, Kaizheng, Veenendaal, Tomas, Wiendels, Maury, Ruiz-Zapata, Alejandra M, van Laar, Justin, Kyranas, Rafail, Enting, Hilde, van Cranenbroek, Bram, Koenen, Hans J P M, Mihaila, Silvia M, Oosterwijk, Egbert, and Kouwer, Paul H J

Abstract

The application of stem cell-derived secretome in regenerative therapies offers the key advantage that instead of the stem cells, only their effective paracrine compounds are in vivo delivered. Ideally, the secretome can be steered by the culture conditions of the stem cells. So far, most studies use stem cells cultured on stiff plastic substrates, not representative of their native 3D environment. In this study, cells are cultured inside synthetic polyisocyanide (PIC)-based hydrogels, which are minimal, tailorable, and highly reproducible biomimetic matrices. Secretome analysis of human adipose-derived stem cells (multiplex, ELISA) displays that matrix manipulation is a powerful tool to direct the secretome composition. As an example, cells in nonadherent PIC gels secrete increased levels of IL-10 and the conditioned media from 3D culture accelerate wound closure. In all, our PIC-based approach opens the door to dedicated matrix design to engineer the secretome for custom applications.

Published
2020

31. Synthetic Extracellular Matrices as a Toolbox to Tune Stem Cell Secretome

Author

Afd Pharmacology, Pharmacology, Liu, Kaizheng, Veenendaal, Tomas, Wiendels, Maury, Ruiz-Zapata, Alejandra M, van Laar, Justin, Kyranas, Rafail, Enting, Hilde, van Cranenbroek, Bram, Koenen, Hans J P M, Mihaila, Silvia M, Oosterwijk, Egbert, Kouwer, Paul H J, Afd Pharmacology, Pharmacology, Liu, Kaizheng, Veenendaal, Tomas, Wiendels, Maury, Ruiz-Zapata, Alejandra M, van Laar, Justin, Kyranas, Rafail, Enting, Hilde, van Cranenbroek, Bram, Koenen, Hans J P M, Mihaila, Silvia M, Oosterwijk, Egbert, and Kouwer, Paul H J

Published
2020

40. Synthetic Semiflexible and Bioactive Brushes

Author

Voerman, Dion, primary, Schluck, Marjolein, additional, Weiden, Jorieke, additional, Joosten, Ben, additional, Eggermont, Loek J., additional, van den Eijnde, Tuur, additional, Ignacio, Bob, additional, Cambi, Alessandra, additional, Figdor, Carl G., additional, Kouwer, Paul H. J., additional, Verdoes, Martijn, additional, Hammink, Roel, additional, and Rowan, Alan E., additional

Published
2019
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42. Smectic A mesophases from luminescent sandic platinum(II) mesogens

Author

Massachusetts Institute of Technology. Department of Chemistry, Swager, Timothy M, Krikorian, Markrete, Voll, Constantin-Chri Alexander, Yoon, Maryam A., Venkatesan, Koushik, Kouwer, Paul H. J., Swager, Timothy M., Massachusetts Institute of Technology. Department of Chemistry, Swager, Timothy M, Krikorian, Markrete, Voll, Constantin-Chri Alexander, Yoon, Maryam A., Venkatesan, Koushik, Kouwer, Paul H. J., and Swager, Timothy M.

Abstract

Square planar platinum(II) thienyl pyridyl complexes with board-shaped structures assemble into lamellar (SmA) liquid crystal phases at elevated temperatures. Liquid crystals of this type are expected to have stronger biaxial correlations than typical calamitic mesogens. The mesophase stability improves with decreasing alkyl chain lengths with C₈H₁₇ having the widest range of stability. All complexes are luminescent in solution., National Science Foundation (U.S.) (Grant DMR-1410718)

Published
2018

43. Tunable Hybrid Matrices Drive Epithelial Morphogenesis and YAP Translocation.

Author

Zhang, Ying, Zegers, Mirjam M. P., Nagelkerke, Anika, Rowan, Alan E., Span, Paul N., and Kouwer, Paul H. J.

Subjects
MORPHOGENESIS, CELL morphology, ETHYLENE glycol, EPITHELIAL cells
Abstract

Morphogenesis is a tightly‐regulated developmental process by which tissues acquire the morphology that is critical to their function. For example, epithelial cells exhibit different 2D and 3D morphologies, induced by distinct biochemical and biophysical cues from their environment. In this work, novel hybrid matrices composed of a Matrigel and synthetic oligo(ethylene glycol)‐grafted polyisocyanides (PICs) hydrogels are used to form a highly tailorable environment. Through precise control of the stiffness and cell‐matrix interactions, while keeping other properties constant, a broad range of morphologies induced in Madin‐Darby Canine Kidney (MDCK) cells is observed. At relatively low matrix stiffness, a large morphological shift from round hollow cysts to 2D monolayers is observed, without concomitant translocation of the mechanotransduction protein Yes‐associated protein (YAP). At higher stiffness levels and enhanced cell‐matrix interactions, tuned by controlling the adhesive peptide density on PIC, the hybrid hydrogels induce a flattened cell morphology with simultaneous YAP translocation, suggesting activation. In 3D cultures, the latter matrices lead to the formation of tubular structures. Thus, mixed synthetic and natural gels, such as the hybrids presented here, are ideal platforms to dissect how external physical factors can be used to regulate morphogenesis in MDCK model system, and in the future, in more complex environments. [ABSTRACT FROM AUTHOR]

Published
2021
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46. Smectic A mesophases from luminescent sandic platinum(II) mesogens

Author

Venkatesan, Koushik, Kouwer, Paul H. J., Swager, Timothy M., Krikorian, Markrete, Voll, Constantin-Chri Alexander, Yoon, Maryam A., Swager, Timothy M, University of Zurich, Swager, Timothy M, Massachusetts Institute of Technology. Department of Chemistry, Krikorian, Markrete, Voll, Constantin-Chri Alexander, and Yoon, Maryam A.

Subjects
10120 Department of Chemistry, Materials science, 3104 Condensed Matter Physics, chemistry.chemical_element, 1600 General Chemistry, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Liquid crystal, 540 Chemistry, Organic chemistry, General Materials Science, Lamellar structure, Alkyl, chemistry.chemical_classification, Molecular Materials, Mesophase, General Chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 2500 General Materials Science, 0104 chemical sciences, Crystallography, chemistry, 0210 nano-technology, Luminescence, Platinum
Abstract

Square planar platinum(II) thienyl pyridyl complexes with board-shaped structures assemble into lamellar (SmA) liquid crystal phases at elevated temperatures. Liquid crystals of this type are expected to have stronger biaxial correlations than typical calamitic mesogens. The mesophase stability improves with decreasing alkyl chain lengths with C₈H₁₇ having the widest range of stability. All complexes are luminescent in solution., National Science Foundation (U.S.) (Grant DMR-1410718)

Published
2016
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47. Strategies To Increase the Thermal Stability of Truly Biomimetic Hydrogels: Combining Hydrophobicity and Directed Hydrogen Bonding

Author

Yuan, Hongbo, primary, Xu, Jialiang, additional, van Dam, Eliane P., additional, Giubertoni, Giulia, additional, Rezus, Yves L. A., additional, Hammink, Roel, additional, Bakker, Huib J., additional, Zhan, Yong, additional, Rowan, Alan E., additional, Xing, Chengfen, additional, and Kouwer, Paul H. J., additional

Published
2017
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