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Mechanotransduction: Relevance to Physical Therapist Practice—Understanding Our Ability to Affect Genetic Expression Through Mechanical Forces

Sharon L. Dunn, Margaret L. Olmedo
DOI: 10.2522/ptj.20150073 Published 1 May 2016
Sharon L. Dunn
S.L. Dunn, PT, PhD, OCS, Department of Physical Therapy, Louisiana State University Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71103 (USA).
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Margaret L. Olmedo
M.L. Olmedo, MD, Department of Orthopaedic Surgery, Louisiana State University Health Sciences Center.
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Figure 2.
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Figure 2.

Focal adhesion complex: a cell matrix binding complex mediated by integrins. A schematic diagram of how forces applied via the ECM (A) or directly to the cell surface (B) travel to integrin-anchored focal adhesions through matrix attachments or cytoskeletal filaments, respectively. Internally generated tension and forces transmitted via cell-cell contact similarly reach focal adhesions through the cytoskeleton. ECM=extracellular matrix; ERK=extracellular signal-regulated kinase, MEK=mitogen activated kinase, Raf and Ras=signaling proteins originally identified in rapidly accelerating fibrosarcoma cells, SOS=Son of Sevenless protein, Grb2=growth factor receptor-bound protein 2, Shc=SH-2 containing adapter protein, FAK=focal adhesion kinase, cav-1=caveloin-1, Vin=vinculin, Pax=paxillin, Tal=talin, GTP/GDP=guanosine tri- and di-phosphate, PK=protein kinase, cAMP=cyclic adenosine monophosphate, ATP=adenosine triphosphate, AC=adenylyl cyclase. Republished with permission of Company of Biologists Ltd from: Ingber DE. Tensegrity II: how structural networks influence cellular information processing networks. J Cell Sci. 2003;116:8; permission conveyed through Copyright Clearance Center Inc.

Figure 1.
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Figure 1.

Mechanosensing cell membrane receptors are responsive to tissue deformation. (Top) Mechanical forces are sensed and transduced at cell-cell, cell-matrix, and cell-lumen interfaces through adhesion complexes, stretch-activated ion channels, or cell surface receptors. The letters “a” through “h” represent the various methods cells use to sense mechanical stimuli: a=stretch activated ion channels open to allow influx or efflux of ions; b=cilia or glycocalyx on the cell surface sense fluid shear or compression; c and d=cell contacts with adjacent cells or ECM allows cells to sense and respond to their local physical environment; e=extracellular proteins within the ECM exert forces on the cell; f=intracellular strain from cytoskeletal components transmits and senses forces across the cell membrane; g=cytoskeletal components adhere to the nuclear envelope to sense cell deformation and alter transcriptional events; and h=intracellular compression affects receptor binding events at the cell surface. (Bottom) Cell surface receptors known to be mechanosensitive include growth factor receptors, integrins, stretch-activated ion channels, and GPCRs. Once stimulated, receptors activate intracellular cytosolic mediators (represented in boxes) to initiate signaling cascades. These cascades may result in nuclear translocation of transcription factors (eg, NFKB), which influence genetic regulation and cell behavior. ECM=extracellular matrix; Wnt=wingless-type signaling pathway; EGF=epidermal growth factor; BMP=bone morphogenic protein; TGFβ=transforming growth factor beta; IGF=insulin growth factor; GPCR=G-protein-coupled receptor; GSK3=glycogen synthase kinase 3; FAK=focal adhesion kinase; ERK=extracellular signal regulated kinase; Akt=protein kinase B; SMAD=a family of signal transduction proteins that respond to TFGβ; Ca2+=calcium; RAS=a family of signal transduction, proteins originally identified and named for rat sarcoma cells; NO=nitrous oxide; PGE2=prostaglandin E2; NF-KB= nuclear factor kappa B; RUNX2=runt-related transcription factor 2; CREB=cyclic AMP response element binding protein; AP1=activator protein 1. Reprinted by permission of Macmillan Publishers Ltd, Nature Publishing Group, from: Bonnet N, Ferrari SL, Exercise and the skeleton: how it works and what it really does. IBMS Bonekey. 2010;7:7. Copyright 2010.

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Vol 96 Issue 5 Table of Contents
Physical Therapy: 96 (5)

Issue highlights

  • Group Versus Individual Physical Therapy for Veterans With Knee Osteoarthritis: Randomized Clinical Trial
  • What Influences Patient-Therapist Interactions in Musculoskeletal Physical Therapy? Qualitative Systematic Review and Meta-Synthesis
  • Identifying Patients With Chronic Low Back Pain Who Respond Best to Mechanical Diagnosis and Therapy: Secondary Analysis of a Randomized Controlled Trial
  • Therapeutic Exercise Training to Reduce Chronic Headache in Working Women: Design of a Randomized Controlled Trial
  • Effects of Nonpharmacological Interventions for Dizziness in Older People: Systematic Review
  • Effects of Cooling During Exercise on Thermoregulatory Responses of Men With Paraplegia
  • Cognitive Contributions to Freezing of Gait in Parkinson Disease: Implications for Physical Rehabilitation
  • Neck Pain and Proprioception Revisited Using the Proprioception Incongruence Detection Test
  • 10-m Shuttle Ride Test in Youth With Osteogenesis Imperfecta Who Use Wheelchairs: Feasibility, Reproducibility, and Physiological Responses
  • Tonic Stretch Reflex Threshold as a Measure of Ankle Plantar-Flexor Spasticity After Stroke
  • Diaphragm Pacing as a Rehabilitative Tool for Patients With Pompe Disease Who Are Ventilator-Dependent: Case Series
  • NF-κB Signaling Pathway in Controlling Intervertebral Disk Cell Response to Inflammatory and Mechanical Stressors
  • Mechanotransduction: Relevance to Physical Therapist Practice—Understanding Our Ability to Affect Genetic Expression Through Mechanical Forces
  • Developmental Biology and Regenerative Medicine: Addressing the Vexing Problem of Persistent Muscle Atrophy in the Chronically Torn Human Rotator Cuff
  • Neural Stem Cell Therapy and Rehabilitation in the Central Nervous System: Emerging Partnerships
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Mechanotransduction: Relevance to Physical Therapist Practice—Understanding Our Ability to Affect Genetic Expression Through Mechanical Forces
Sharon L. Dunn, Margaret L. Olmedo
Physical Therapy May 2016, 96 (5) 712-721; DOI: 10.2522/ptj.20150073

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Mechanotransduction: Relevance to Physical Therapist Practice—Understanding Our Ability to Affect Genetic Expression Through Mechanical Forces
Sharon L. Dunn, Margaret L. Olmedo
Physical Therapy May 2016, 96 (5) 712-721; DOI: 10.2522/ptj.20150073
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  • Article
    • Abstract
    • Mechanotransduction: Defined
    • Cells Known to Be Influenced by Mechanotransduction
    • Molecular Biology
    • Receptors of Mechanical Stimuli
    • Downstream Cellular Effects of Mechanical Stimulation
    • Role of the Extracellular Matrix
    • Load Responsiveness
    • Load Specificity
    • Shear and Endothelial Cells
    • Tension and Lung Tissue
    • Compression, Distraction, and Bone
    • Multiple Forces and Cartilage
    • Tension and Skeletal Muscle
    • Tension and Tendon
    • Tension and Skin
    • Importance of Physiologic Loads to Tissue Integrity in Health and Use of Precise Loads in Repair
    • Conclusions
    • Footnotes
    • References
  • Figures & Data
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  • PDF

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Subjects

  • Perspectives
  • Special Series and Special Issues
    • Special Series on Regenerative Rehabilitation and Genomics
  • Neurology/Neuromuscular System
    • Anatomy: Central Nervous System and Neuromuscular System
  • Musculoskeletal System/Orthopedic
    • Musculoskeletal System/Orthopedic: Other
    • Anatomy and Physiology: Musculoskeletal System

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