Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor Spheroids

Abstract Supramolecular assemblies found in nature demonstrate the concept of creating functionality through structure formation. In recent years, these complex natural architectures have inspired the development of materials for the formation of synthetic nanostructures within living cells. These i...

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Main Authors: Sarah Chagri, Konrad Maxeiner, Maria J. S. A. Silva, Lisa Förch, Julian Link, Patrick Roth, Raphael Meyer, Jana Fetzer, Anke Kaltbeitzel, Ingo Lieberwirth, Katharina Landfester, Manfred Wagner, David Y.W. Ng, Tanja Weil
Format: Article
Language:English
Published: Wiley 2025-07-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202412606
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author Sarah Chagri
Konrad Maxeiner
Maria J. S. A. Silva
Lisa Förch
Julian Link
Patrick Roth
Raphael Meyer
Jana Fetzer
Anke Kaltbeitzel
Ingo Lieberwirth
Katharina Landfester
Manfred Wagner
David Y.W. Ng
Tanja Weil
author_facet Sarah Chagri
Konrad Maxeiner
Maria J. S. A. Silva
Lisa Förch
Julian Link
Patrick Roth
Raphael Meyer
Jana Fetzer
Anke Kaltbeitzel
Ingo Lieberwirth
Katharina Landfester
Manfred Wagner
David Y.W. Ng
Tanja Weil
author_sort Sarah Chagri
collection DOAJ
description Abstract Supramolecular assemblies found in nature demonstrate the concept of creating functionality through structure formation. In recent years, these complex natural architectures have inspired the development of materials for the formation of synthetic nanostructures within living cells. These intracellular assemblies have the potential to modulate cellular processes, yet their specific effects on cellular metabolism and 3D cell networks, such as tumor spheroids, still remain underexplored. Herein, the study correlates the glutathione‐induced formation of synthetic nanostructures inside MDA‐MB‐231 triple‐negative breast cancer cells to the metabolic disruption and mitochondrial degradation observed in 2D cell culture, as well as to cell death and size decrease in a 3D tumor spheroid model. In 2D cell culture, material‐cell interactions are examined through live‐cell imaging and by quantifying changes in mitochondrial respiration. By studying the interplay between glutathione‐responsive cytosolic peptide assembly and the implications on the integrity of the mitochondrial network, as well as on 3D cell networks, the work advances the understanding of how synthetic intracellular nanofibers impact vital functions of living cells.
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spelling doaj-art-46d5134bb6ef489e95f6bcce7d8bbf8e2025-08-20T03:15:35ZengWileyAdvanced Science2198-38442025-07-011225n/an/a10.1002/advs.202412606Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor SpheroidsSarah Chagri0Konrad Maxeiner1Maria J. S. A. Silva2Lisa Förch3Julian Link4Patrick Roth5Raphael Meyer6Jana Fetzer7Anke Kaltbeitzel8Ingo Lieberwirth9Katharina Landfester10Manfred Wagner11David Y.W. Ng12Tanja Weil13Max Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyMax Planck Institute for Polymer Research 55128 Mainz GermanyAbstract Supramolecular assemblies found in nature demonstrate the concept of creating functionality through structure formation. In recent years, these complex natural architectures have inspired the development of materials for the formation of synthetic nanostructures within living cells. These intracellular assemblies have the potential to modulate cellular processes, yet their specific effects on cellular metabolism and 3D cell networks, such as tumor spheroids, still remain underexplored. Herein, the study correlates the glutathione‐induced formation of synthetic nanostructures inside MDA‐MB‐231 triple‐negative breast cancer cells to the metabolic disruption and mitochondrial degradation observed in 2D cell culture, as well as to cell death and size decrease in a 3D tumor spheroid model. In 2D cell culture, material‐cell interactions are examined through live‐cell imaging and by quantifying changes in mitochondrial respiration. By studying the interplay between glutathione‐responsive cytosolic peptide assembly and the implications on the integrity of the mitochondrial network, as well as on 3D cell networks, the work advances the understanding of how synthetic intracellular nanofibers impact vital functions of living cells.https://doi.org/10.1002/advs.202412606bioresponsive nanomaterialsmitochondrial disruptionpeptide nanostructuressupramolecular assembliessynthetic intracellular nanostructurestumor spheroids
spellingShingle Sarah Chagri
Konrad Maxeiner
Maria J. S. A. Silva
Lisa Förch
Julian Link
Patrick Roth
Raphael Meyer
Jana Fetzer
Anke Kaltbeitzel
Ingo Lieberwirth
Katharina Landfester
Manfred Wagner
David Y.W. Ng
Tanja Weil
Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor Spheroids
Advanced Science
bioresponsive nanomaterials
mitochondrial disruption
peptide nanostructures
supramolecular assemblies
synthetic intracellular nanostructures
tumor spheroids
title Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor Spheroids
title_full Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor Spheroids
title_fullStr Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor Spheroids
title_full_unstemmed Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor Spheroids
title_short Intracellular Formation of Synthetic Peptide Nanostructures Causes Mitochondrial Disruption and Cell Death in Tumor Spheroids
title_sort intracellular formation of synthetic peptide nanostructures causes mitochondrial disruption and cell death in tumor spheroids
topic bioresponsive nanomaterials
mitochondrial disruption
peptide nanostructures
supramolecular assemblies
synthetic intracellular nanostructures
tumor spheroids
url https://doi.org/10.1002/advs.202412606
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