Matrix-induced nuclear remodeling and mechano-therapeutics

Summary: The extracellular matrix (ECM) provides structural support and mechanical cues that profoundly influence cellular behavior via nuclear mechanotransduction. This review discusses how ECM biophysical properties, including stiffness, topology, and spatial confinement, regulate nuclear mechanic...

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Main Authors: Jung-Hwan Lee, Yeo Gyun Yun, Hae-Won Kim
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725009477
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author Jung-Hwan Lee
Yeo Gyun Yun
Hae-Won Kim
author_facet Jung-Hwan Lee
Yeo Gyun Yun
Hae-Won Kim
author_sort Jung-Hwan Lee
collection DOAJ
description Summary: The extracellular matrix (ECM) provides structural support and mechanical cues that profoundly influence cellular behavior via nuclear mechanotransduction. This review discusses how ECM biophysical properties, including stiffness, topology, and spatial confinement, regulate nuclear mechanics and chromatin organization to determine cell fate across diverse pathophysiological contexts. We describe how mechanical signals propagate from the plasma membrane through cytoskeletal networks to modulate nuclear envelope tension, chromatin accessibility, and epigenetic landscapes. These matrix-driven nuclear changes orchestrate cellular responses in cancer progression, inflammation, fibrosis, stem cell differentiation, and age-related tissue dysfunction. Building on this mechanistic insight, we highlight emerging therapeutic strategies targeting the matrix-nucleus axis, such as tuning matrix properties to modulate chromatin accessibility, mechano-priming cells to enhance therapeutic outcomes, and targeting mechanosensitive molecules in the cytoskeletal-nuclear interface. Collectively, these approaches represent a promising paradigm leveraging mechanically induced epigenetic regulation and nuclear mechanobiology for disease treatment and tissue regeneration.
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spelling doaj-art-c5fb6dc828f04c8297da7055cb78ca532025-08-24T05:12:07ZengElsevierCell Reports2211-12472025-09-0144911617610.1016/j.celrep.2025.116176Matrix-induced nuclear remodeling and mechano-therapeuticsJung-Hwan Lee0Yeo Gyun Yun1Hae-Won Kim2Intitute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan 31116, Republic of KoreaIntitute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan 31116, Republic of KoreaIntitute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan 31116, Republic of Korea; Corresponding authorSummary: The extracellular matrix (ECM) provides structural support and mechanical cues that profoundly influence cellular behavior via nuclear mechanotransduction. This review discusses how ECM biophysical properties, including stiffness, topology, and spatial confinement, regulate nuclear mechanics and chromatin organization to determine cell fate across diverse pathophysiological contexts. We describe how mechanical signals propagate from the plasma membrane through cytoskeletal networks to modulate nuclear envelope tension, chromatin accessibility, and epigenetic landscapes. These matrix-driven nuclear changes orchestrate cellular responses in cancer progression, inflammation, fibrosis, stem cell differentiation, and age-related tissue dysfunction. Building on this mechanistic insight, we highlight emerging therapeutic strategies targeting the matrix-nucleus axis, such as tuning matrix properties to modulate chromatin accessibility, mechano-priming cells to enhance therapeutic outcomes, and targeting mechanosensitive molecules in the cytoskeletal-nuclear interface. Collectively, these approaches represent a promising paradigm leveraging mechanically induced epigenetic regulation and nuclear mechanobiology for disease treatment and tissue regeneration.http://www.sciencedirect.com/science/article/pii/S2211124725009477CP: Cell biology
spellingShingle Jung-Hwan Lee
Yeo Gyun Yun
Hae-Won Kim
Matrix-induced nuclear remodeling and mechano-therapeutics
Cell Reports
CP: Cell biology
title Matrix-induced nuclear remodeling and mechano-therapeutics
title_full Matrix-induced nuclear remodeling and mechano-therapeutics
title_fullStr Matrix-induced nuclear remodeling and mechano-therapeutics
title_full_unstemmed Matrix-induced nuclear remodeling and mechano-therapeutics
title_short Matrix-induced nuclear remodeling and mechano-therapeutics
title_sort matrix induced nuclear remodeling and mechano therapeutics
topic CP: Cell biology
url http://www.sciencedirect.com/science/article/pii/S2211124725009477
work_keys_str_mv AT junghwanlee matrixinducednuclearremodelingandmechanotherapeutics
AT yeogyunyun matrixinducednuclearremodelingandmechanotherapeutics
AT haewonkim matrixinducednuclearremodelingandmechanotherapeutics