ArticleProceedings of the National Academy of Sciences of the United States of America2024
Hydrogel biomaterials that stiffen and soften on demand reveal that skeletal muscle stem cells harbor a mechanical memory.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Review
- Mechanical regulation of cell memory.Nature structural & molecular biology · 2026Review
- Hydrogel-Based Systems in Intrauterine Adhesions: Bridging the Gap from Bench to Bedside.Advanced healthcare materials · 2026Review
- Mechanical Intelligence in Bone Regeneration: Bridging Material and Cellular Memory for Enhanced Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Reversible Mechano-Regulation of Cellular Senescence: Effects of Substrate Stiffness on Cells.Cells · 2026Article
- Beyond Potency: Emerging Determinants and Optimization Strategies Enhancing Therapeutic Efficacy of Adult Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Using biomaterial-based 3D in vitro cancer models to solve current clinical problems.British journal of cancer · 2026Review
- Mechanobiological landscape of muscle stem cells.Skeletal muscle · 2026Review
- Adhesive hydrogel delivering ALA prevents the malignant transformation of oral leukoplakia.Materials today. Bio · 2026Article
- Single-Cell Transcriptomic Analysis of Salivary Epithelial Cells Reveals Large-Scale Dysregulation in Bitter Taste Dysfunction.International journal of molecular sciences · 2026Article
- The Synthetic Extracellular Matrix as a Maestro of the In Vitro Stem Cell Niche: Orchestrating Fate and Function.Biomedicines · 2026Review
- Matrix Stiffness-Induced Mechanical Memory of Periodontal Ligament Cell Promotes Osteogenesis in Periodontal Bone Repair.International dental journal · 2026Article
- Mechanical memory in cells: mechanisms, effects, and applications in regenerative medicine.Frontiers in bioengineering and biotechnology · 2026Review
- Cell Surface Thiol Engineering Mechanoregulates Myogenic Differentiation via the FAK-PI3K-AKT Axis.Advanced healthcare materials · 2026Article
- A scaffold based on uncoated rice grains integrated with piscine cells supporting the production of a sustainable food.NPJ science of food · 2025Article
- Biomaterial-mediated Cell Atlas: an insight from single-cell and spatial transcriptomics.Bioactive materials · 2025Review
- Mechanomemory after short episodes of intermittent stresses induces YAP translocation via increasing F-actin.APL bioengineering · 2025Article
- 3D Mechanical Confinement Directs Muscle Stem Cell Fate and Function.Advanced biology · 2025Article
- Single-cell transcriptional profiling reveals developmental dynamics of longissimus dorsi muscle in adult and Juvenile bactrian camels.Frontiers in physiology · 2025Article
- Hydrogel biomaterials that stiffen and soften on demand reveal that skeletal muscle stem cells harbor a mechanical memory.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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9 authors.
Funding
Abstract
Muscle stem cells (MuSCs) are specialized cells that reside in adult skeletal muscle poised to repair muscle tissue. The ability of MuSCs to regenerate damaged tissues declines markedly with aging and in diseases such as Duchenne muscular dystrophy, but the underlying causes of MuSC dysfunction remain poorly understood. Both aging and disease result in dramatic increases in the stiffness of the muscle tissue microenvironment from fibrosis. MuSCs are known to lose their regenerative potential if cultured on stiff plastic substrates. We sought to determine whether MuSCs harbor a memory of their past microenvironment and if it can be overcome. We tested MuSCs in situ using dynamic hydrogel biomaterials that soften or stiffen on demand in response to light and found that freshly isolated MuSCs develop a persistent memory of substrate stiffness characterized by loss of proliferative progenitors within the first three days of culture on stiff substrates. MuSCs cultured on soft hydrogels had altered cytoskeletal organization and activity of Rho and Rac guanosine triphosphate hydrolase (GTPase) and Yes-associated protein mechanotransduction pathways compared to those on stiff hydrogels. Pharmacologic inhibition identified RhoA activation as responsible for the mechanical memory phenotype, and single-cell RNA sequencing revealed a molecular signature of the mechanical memory. These studies highlight that microenvironmental stiffness regulates MuSC fate and leads to MuSC dysfunction that is not readily reversed by changing stiffness. Our results suggest that stiffness can be circumvented by targeting downstream signaling pathways to overcome stem cell dysfunction in aged and disease states with aberrant fibrotic tissue mechanics.
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