Cell-derived lactate triggers local hydrogelation and phenotype remodelling
Nature Communications, vol. 17
Abstract
Many tumours release lactate as a major metabolic product and signalling molecule. Here we use lactate flux as an endogenous trigger for covalent hydrogel formation. Phenol-functionalised alginate remains soluble until cell-derived lactate is oxidised by lactate oxidase; the generated hydrogen peroxide is used by horseradish peroxidase to crosslink phenols and form a matrix at metabolically active sites. Hydrogels form within minutes and reach storage moduli from approximately 10 Pa to 5 kPa. In tumour-spheroid models, including a patient-derived glioblastoma spheroid model, local lactate production generates spatially confined gelation that extended up to around 1 mm from the spheroid surface. Nanoindentation and fluorescence correlation spectroscopy reveal radial stiffness and polymer-density gradients, while proteome profiling and imaging indicate reduced proliferative signalling and increased markers associated with migration and matrix remodelling. These findings establish metabolite-gated hydrogelation as a strategy to couple cellular metabolism to covalent matrix assembly, mechanics and transport, providing a bio-synthetic platform for modelling cell-matrix reciprocity and tumour confinement.
Authors 13
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Max Planck Institute for Polymer Research
Affiliation as printed
Max Planck Institute for Polymer Research, Mainz, Germany
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Tom C. Schneider Aachen DWI - Leibniz Institute for Interactive Materials Institute of Applied Medical Engineering Department of Advanced Materials for Biomedicine Institute of Technical and Macromolecular Chemistry Chair of Macromolecular Materials for Medicine
DWI – Leibniz Institute for Interactive Materials · Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
DWI-Leibniz Institute for Interactive Materials, Aachen, Germany
Institute of Applied Medical Engineering (AME), Department of Advanced Materials for Biomedicine (AMB), University Hospital RWTH Aachen, Center for Biohybrid Medical Systems (CMBS), Aachen, Germany
Institute of Technical and Macromolecular Chemistry (ITMC), Chair of Macromolecular Materials for Medicine, RWTH Aachen University, Aachen, Germany
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Max Planck Institute for Polymer Research
Affiliation as printed
Max Planck Institute for Polymer Research, Mainz, Germany
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Johannes Gutenberg University Mainz
Affiliation as printed
Institute for Developmental Biology and Neurobiology, Johannes Gutenberg University, Mainz, Germany
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Max Planck Institute for Polymer Research
Affiliation as printed
Max Planck Institute for Polymer Research, Mainz, Germany
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Max Planck Institute for Polymer Research
Affiliation as printed
Max Planck Institute for Polymer Research, Mainz, Germany
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Max Planck Institute for Polymer Research · Max Planck School Matter to Life
Affiliation as printed
Max Planck Institute for Polymer Research, Mainz, Germany
Max Planck School Matter to Life, Heidelberg, Germany
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Max Planck Institute for Polymer Research
Affiliation as printed
Max Planck Institute for Polymer Research, Mainz, Germany
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Max Planck Institute for Polymer Research
Affiliation as printed
Max Planck Institute for Polymer Research, Mainz, Germany
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Johannes Gutenberg University Mainz
Affiliation as printed
Institute for Developmental Biology and Neurobiology, Johannes Gutenberg University, Mainz, Germany
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Laura De Laporte Aachen DWI - Leibniz Institute for Interactive Materials Institute of Applied Medical Engineering Department of Advanced Materials for Biomedicine Institute of Technical and Macromolecular Chemistry Chair of Macromolecular Materials for Medicine
DWI – Leibniz Institute for Interactive Materials · Universitätsklinikum Aachen · Max Planck School Matter to Life · RWTH Aachen University
Affiliation as printed
DWI-Leibniz Institute for Interactive Materials, Aachen, Germany
Institute of Applied Medical Engineering (AME), Department of Advanced Materials for Biomedicine (AMB), University Hospital RWTH Aachen, Center for Biohybrid Medical Systems (CMBS), Aachen, Germany
Institute of Technical and Macromolecular Chemistry (ITMC), Chair of Macromolecular Materials for Medicine, RWTH Aachen University, Aachen, Germany
Max Planck School Matter to Life, Heidelberg, Germany
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David Y.W. Ng corresponding
Max Planck Institute for Polymer Research
Affiliation as printed
Max Planck Institute for Polymer Research, Mainz, Germany. david.ng@mpip-mainz.mpg.de
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Tanja Weil corresponding
Max Planck Institute for Polymer Research · Max Planck School Matter to Life
Affiliation as printed
Max Planck Institute for Polymer Research, Mainz, Germany. weil@mpip-mainz.mpg.de
Max Planck School Matter to Life, Heidelberg, Germany. weil@mpip-mainz.mpg.de
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