ArticleStem cells (Dayton, Ohio)2015
Cell Mechanosensitivity to Extremely Low-Magnitude Signals Is Enabled by a LINCed Nucleus.
Article in Stem cells (Dayton, Ohio), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
90 citing papers in PubMed, 160 citations in OpenAlex.
- The Efficacy of Low-intensity Vibration to Improve Bone Health in Patients with End-stage Renal Disease Is Highly Dependent on Compliance and Muscle Response.Academic radiology · 2017Trial
- Effect of Low-Magnitude, High-Frequency Mechanical Stimulation on BMD Among Young Childhood Cancer Survivors: A Randomized Clinical Trial.JAMA oncology · 2016Trial
- Effect of Low-Magnitude Mechanical Stimuli on Bone Density and Structure in Pediatric Crohn's Disease: A Randomized Placebo-Controlled Trial.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Trial
- Biological mechanisms underlying the effects of low-magnitude mechanical stress in osteoporosis (Review).Experimental and therapeutic medicine · 2026Review
- Low intensity vibration with zoledronate reduces musculoskeletal weakness and adiposity in estrogen deprived female mice.Nature communications · 2026Article
- The dual guardians of cellular stability: exploring nesprin and lamin in senescence.Cell death & disease · 2025Review
- The LINC Complex Regulates Tendon Elastic Modulus, Collagen Crimp, and Lateral Expansion During Early Postnatal Development.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025Article
- Small Accelerations of the cell generate sufficient nuclear motion to modulate transcriptional activity, driving cellular response independent of matrix strain.bioRxiv : the preprint server for biology · 2025Article
- Depletion of SUN1/2 induces heterochromatin accrual in mesenchymal stem cells during adipogenesis.Communications biology · 2025Article
- Increased deformations are dispensable for encapsulated cell mechanoresponse in engineered bone analogs mimicking aging bone marrow.Mechanobiology in medicine · 2025Article
- Role of the cytoskeleton in cellular reprogramming: effects of biophysical and biochemical factors.Frontiers in molecular biosciences · 2025Review
- Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields.Mechanobiology in medicine · 2024Article
- Dynamic strain and β-catenin mediated suppression of interferon responsive genes in quiescent mesenchymal stromal/stem cells.Biochemistry and biophysics reports · 2024Article
- Combined Effects of Cyclic Hypoxic and Mechanical Stimuli on Human Bone Marrow Mesenchymal Stem Cell Differentiation: A New Approach to the Treatment of Bone Loss.Journal of clinical medicine · 2024Article
- Osterix-driven LINC complex disruption in vivo diminishes osteogenesis at 8 weeks but not at 15 weeks.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2024Article
- Sound Matrix Shaping of Living Matter: From Macrosystems to Cell Microenvironment, Where Mitochondria Act as Energy Portals in Detecting and Processing Sound Vibrations.International journal of molecular sciences · 2024Review
- Data-Driven and Cell-Specific Determination of Nuclei-Associated Actin Structure.Small structures · 2024Article
- Prrx1-driven LINC complex disruption in vivo reduces osteoid deposition but not bone quality after voluntary wheel running.bioRxiv : the preprint server for biology · 2024Article
- The roles of Hippo/YAP signaling pathway in physical therapy.Cell death discovery · 2024Review
- Prrx1-driven LINC complex disruption in vivo reduces osteoid deposition but not bone quality after voluntary wheel running.PloS one · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
A cell's ability to recognize and adapt to the physical environment is central to its survival and function, but how mechanical cues are perceived and transduced into intracellular signals remains unclear. In mesenchymal stem cells (MSCs), high-magnitude substrate strain (HMS, ≥2%) effectively suppresses adipogenesis via induction of focal adhesion (FA) kinase (FAK)/mTORC2/Akt signaling generated at FAs. Physiologic systems also rely on a persistent barrage of low-level signals to regulate behavior. Exposing MSC to extremely low-magnitude mechanical signals (LMS) suppresses adipocyte formation despite the virtual absence of substrate strain (<0.001%), suggesting that LMS-induced dynamic accelerations can generate force within the cell. Here, we show that MSC response to LMS is enabled through mechanical coupling between the cytoskeleton and the nucleus, in turn activating FAK and Akt signaling followed by FAK-dependent induction of RhoA. While LMS and HMS synergistically regulated FAK activity at the FAs, LMS-induced actin remodeling was concentrated at the perinuclear domain. Preventing nuclear-actin cytoskeleton mechanocoupling by disrupting linker of nucleoskeleton and cytoskeleton (LINC) complexes inhibited these LMS-induced signals as well as prevented LMS repression of adipogenic differentiation, highlighting that LINC connections are critical for sensing LMS. In contrast, FAK activation by HMS was unaffected by LINC decoupling, consistent with signal initiation at the FA mechanosome. These results indicate that the MSC responds to its dynamic physical environment not only with "outside-in" signaling initiated by substrate strain, but vibratory signals enacted through the LINC complex enable matrix independent "inside-inside" signaling.
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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.