The load-bearing mechanosome revisited

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

We introduced the mechanosome hypothesis in 2003 as a heuristic model for investigating mechanotransduction in bone (Pavalko et al., J Cell Biochem, 2003, 88(1):104-112). This model suggested specific approaches for investigating how mechanical information is conveyed from the membrane of the sensor bone cell to the target genes and how this transmitted information from the membrane is converted into changes in transcription. The key concepts underlying the mechanosome hypothesis are that load-induced deformation of bone deforms the sensor cell membrane; embedded in the membrane are the focal adhesion and cadherin-catenin complexes, which in turn are physically connected to the chromatin via a solid-state scaffold. The physical stimulation of the membrane launches multiprotein complexes (mechanosomes) from the adhesion platforms while concomitantly tugging target genes into position for contact with the incoming mechanosomes, the carriers of the mechanical information to the nucleus. The mechanosome is comprised of an adhesion-associated protein and a nucleocytoplasmic shuttling transcription factor. Upon arrival at the target gene, mechanosomes alter DNA conformation and thus influence the interactions between trans-acting proteins along the gene, changing gene activity. Here, we update significant progress related to the mechanosome concept since publication of our original hypothesis. The launching of adhesion- and cytoskeletal- associated proteins into the nucleus toward target genes appears to be a common mechanism for regulating cell response to changes in its mechanical microenvironment.

Original languageEnglish
Pages (from-to)213-223
Number of pages11
JournalClinical Reviews in Bone and Mineral Metabolism
Volume8
Issue number4
DOIs
StatePublished - Dec 2010

Fingerprint

Weight-Bearing
Membranes
Bone and Bones
Genes
Physical Stimulation
Nucleic Acid Conformation
Multiprotein Complexes
Catenins
Focal Adhesions
Gene Order
Cytoskeletal Proteins
Cadherins
Chromatin
Publications
Proteins
Transcription Factors
Cell Membrane

Keywords

  • β-Catenin
  • Adhesion
  • Bone
  • Cadherin
  • Cytoskeleton
  • FAK
  • Integrin
  • Mechanotransduction

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

The load-bearing mechanosome revisited. / Bidwell, Joseph; Pavalko, Fredrick.

In: Clinical Reviews in Bone and Mineral Metabolism, Vol. 8, No. 4, 12.2010, p. 213-223.

Research output: Contribution to journalArticle

@article{d5efb0641ba1425f817b12d00b152762,
title = "The load-bearing mechanosome revisited",
abstract = "We introduced the mechanosome hypothesis in 2003 as a heuristic model for investigating mechanotransduction in bone (Pavalko et al., J Cell Biochem, 2003, 88(1):104-112). This model suggested specific approaches for investigating how mechanical information is conveyed from the membrane of the sensor bone cell to the target genes and how this transmitted information from the membrane is converted into changes in transcription. The key concepts underlying the mechanosome hypothesis are that load-induced deformation of bone deforms the sensor cell membrane; embedded in the membrane are the focal adhesion and cadherin-catenin complexes, which in turn are physically connected to the chromatin via a solid-state scaffold. The physical stimulation of the membrane launches multiprotein complexes (mechanosomes) from the adhesion platforms while concomitantly tugging target genes into position for contact with the incoming mechanosomes, the carriers of the mechanical information to the nucleus. The mechanosome is comprised of an adhesion-associated protein and a nucleocytoplasmic shuttling transcription factor. Upon arrival at the target gene, mechanosomes alter DNA conformation and thus influence the interactions between trans-acting proteins along the gene, changing gene activity. Here, we update significant progress related to the mechanosome concept since publication of our original hypothesis. The launching of adhesion- and cytoskeletal- associated proteins into the nucleus toward target genes appears to be a common mechanism for regulating cell response to changes in its mechanical microenvironment.",
keywords = "β-Catenin, Adhesion, Bone, Cadherin, Cytoskeleton, FAK, Integrin, Mechanotransduction",
author = "Joseph Bidwell and Fredrick Pavalko",
year = "2010",
month = "12",
doi = "10.1007/s12018-010-9075-1",
language = "English",
volume = "8",
pages = "213--223",
journal = "Clinical Reviews in Bone and Mineral Metabolism",
issn = "1534-8644",
publisher = "Humana Press",
number = "4",

}

TY - JOUR

T1 - The load-bearing mechanosome revisited

AU - Bidwell, Joseph

AU - Pavalko, Fredrick

PY - 2010/12

Y1 - 2010/12

N2 - We introduced the mechanosome hypothesis in 2003 as a heuristic model for investigating mechanotransduction in bone (Pavalko et al., J Cell Biochem, 2003, 88(1):104-112). This model suggested specific approaches for investigating how mechanical information is conveyed from the membrane of the sensor bone cell to the target genes and how this transmitted information from the membrane is converted into changes in transcription. The key concepts underlying the mechanosome hypothesis are that load-induced deformation of bone deforms the sensor cell membrane; embedded in the membrane are the focal adhesion and cadherin-catenin complexes, which in turn are physically connected to the chromatin via a solid-state scaffold. The physical stimulation of the membrane launches multiprotein complexes (mechanosomes) from the adhesion platforms while concomitantly tugging target genes into position for contact with the incoming mechanosomes, the carriers of the mechanical information to the nucleus. The mechanosome is comprised of an adhesion-associated protein and a nucleocytoplasmic shuttling transcription factor. Upon arrival at the target gene, mechanosomes alter DNA conformation and thus influence the interactions between trans-acting proteins along the gene, changing gene activity. Here, we update significant progress related to the mechanosome concept since publication of our original hypothesis. The launching of adhesion- and cytoskeletal- associated proteins into the nucleus toward target genes appears to be a common mechanism for regulating cell response to changes in its mechanical microenvironment.

AB - We introduced the mechanosome hypothesis in 2003 as a heuristic model for investigating mechanotransduction in bone (Pavalko et al., J Cell Biochem, 2003, 88(1):104-112). This model suggested specific approaches for investigating how mechanical information is conveyed from the membrane of the sensor bone cell to the target genes and how this transmitted information from the membrane is converted into changes in transcription. The key concepts underlying the mechanosome hypothesis are that load-induced deformation of bone deforms the sensor cell membrane; embedded in the membrane are the focal adhesion and cadherin-catenin complexes, which in turn are physically connected to the chromatin via a solid-state scaffold. The physical stimulation of the membrane launches multiprotein complexes (mechanosomes) from the adhesion platforms while concomitantly tugging target genes into position for contact with the incoming mechanosomes, the carriers of the mechanical information to the nucleus. The mechanosome is comprised of an adhesion-associated protein and a nucleocytoplasmic shuttling transcription factor. Upon arrival at the target gene, mechanosomes alter DNA conformation and thus influence the interactions between trans-acting proteins along the gene, changing gene activity. Here, we update significant progress related to the mechanosome concept since publication of our original hypothesis. The launching of adhesion- and cytoskeletal- associated proteins into the nucleus toward target genes appears to be a common mechanism for regulating cell response to changes in its mechanical microenvironment.

KW - β-Catenin

KW - Adhesion

KW - Bone

KW - Cadherin

KW - Cytoskeleton

KW - FAK

KW - Integrin

KW - Mechanotransduction

UR - http://www.scopus.com/inward/record.url?scp=79960113642&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960113642&partnerID=8YFLogxK

U2 - 10.1007/s12018-010-9075-1

DO - 10.1007/s12018-010-9075-1

M3 - Article

AN - SCOPUS:79960113642

VL - 8

SP - 213

EP - 223

JO - Clinical Reviews in Bone and Mineral Metabolism

JF - Clinical Reviews in Bone and Mineral Metabolism

SN - 1534-8644

IS - 4

ER -