ArticleBMC systems biology2017
A mathematical model of mechanotransduction reveals how mechanical memory regulates mesenchymal stem cell fate decisions.
Article in BMC systems biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
- Mechanical Intelligence in Bone Regeneration: Bridging Material and Cellular Memory for Enhanced Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A Circuit of Mechanically Regulated Transcription Factors Balances Regenerative and Fibrotic Memory of Mesenchymal Stromal Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Programmable Microcarriers for Stem Cell Therapy: Advanced Fabrication Strategies, Stem Cell Fate Regulatory Function and Biomedical Applications.International journal of molecular sciences · 2026Review
- Mechanical forces orchestrate the epigenetic landscape of oral mesenchymal stem/progenitor cell fate in dental and periodontal tissues.Frontiers in cell and developmental biology · 2026Review
- Mechanical memory in cells: mechanisms, effects, and applications in regenerative medicine.Frontiers in bioengineering and biotechnology · 2026Review
- A Mathematical Model of Wound Healing Incorporating Strain-Induced MSC Differentiation.Annals of biomedical engineering · 2026Article
- From Light to Life: Molecular Mechanisms and Macroscopic Transformations in Photoresponsive Hydrogels.Polymer science & technology (Washington, D.C.) · 2025Review
- Review
- Cellular mechanical memory: a potential tool for mesenchymal stem cell-based therapy.Stem cell research & therapy · 2025Review
- Cell-matrix feedback controls stretch-induced cellular memory and fibroblast activation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Role of YAP/TAZ in bone diseases: A transductor from mechanics to biology.Journal of orthopaedic translation · 2025Review
- Divergence in cellular markers observed in single-cell transcriptomics datasets between cultured primary trabecular meshwork cells and tissues.Scientific data · 2025Article
- To be or not to be - Decoding the Trabecular Meshwork Cell Identity.bioRxiv : the preprint server for biology · 2024Article
- Microfluidically Aligned Collagen to Maintain the Phenotype of Tenocytes In Vitro.Advanced healthcare materials · 2024Article
- Implications of Cellular Mechanical Memory in Bioengineering.ACS biomaterials science & engineering · 2023Review
- A cost-effective and enhanced mesenchymal stem cell expansion platform with internal plasma-activated biofunctional interfaces.Materials today. Bio · 2023Article
- Characterization of extracellular matrix deposited by segmental trabecular meshwork cells.Experimental eye research · 2023Article
- Substrate topographies modulate the secretory activity of human bone marrow mesenchymal stem cells.Stem cell research & therapy · 2023Article
- Characterization of extracellular matrix deposited by segmental trabecular meshwork cells.bioRxiv : the preprint server for biology · 2023Article
- Mechanobiology: A landscape for reinterpreting stem cell heterogeneity and regenerative potential in diseased tissues.iScience · 2023Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMechanical and biophysical properties of the cellular microenvironment regulate cell fate decisions. Mesenchymal stem cell (MSC) fate is influenced by past mechanical dosing (memory), but the mechanisms underlying this process have not yet been well defined. We have yet to understand how memory affects specific cell fate decisions, such as the differentiation of MSCs into neurons, adipocytes, myocytes, and osteoblasts.
resultsWe study a minimal gene regulatory network permissive of multi-lineage MSC differentiation into four cell fates. We present a continuous model that is able to describe the cell fate transitions that occur during differentiation, and analyze its dynamics with tools from multistability, bifurcation, and cell fate landscape analysis, and via stochastic simulation. Whereas experimentally, memory has only been observed during osteogenic differentiation, this model predicts that memory regions can exist for each of the four MSC-derived cell lineages. We can predict the substrate stiffness ranges over which memory drives differentiation; these are directly testable in an experimental setting. Furthermore, we quantitatively predict how substrate stiffness and culture duration co-regulate the fate of a stem cell, and we find that the feedbacks from the differentiating MSC onto its substrate are critical to preserve mechanical memory. Strikingly, we show that re-seeding MSCs onto a sufficiently soft substrate increases the number of cell fates accessible.
conclusionsControl of MSC differentiation is crucial for the success of much-lauded regenerative therapies based on MSCs. We have predicted new memory regions that will directly impact this control, and have quantified the size of the memory region for osteoblasts, as well as the co-regulatory effects on cell fates of substrate stiffness and culture duration. Taken together, these results can be used to develop novel strategies to better control the fates of MSCs in vitro and following transplantation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.