A model for the role of integrins in flow induced mechanotransduction in osteocytes
Wang, Yilin, McNamara, Laoise M., Schaffler, Mitchell B. and Weinbaum, Sheldon (2007) A model for the role of integrins in flow induced mechanotransduction in osteocytes. Proceedings of the National Academy of Sciences of the United States of America, 104, (40), 15941-15946. (doi:10.1073/pnas.0707246104).
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A fundamental paradox in bone mechanobiology is that tissuelevel
strains caused by human locomotion are too small to initiate intracellular signaling in osteocytes. A cellular-level strainamplification
model previously has been proposed to explain this paradox. However, the molecular mechanism for initiating signaling
has eluded detection because none of the molecules in this
previously proposed model are known mediators of intracellular
signaling. In this paper, we explore a paradigm and quantitative
model for the initiation of intracellular signaling, namely that the
processes are attached directly at discrete locations along the
canalicular wall by beta3 integrins at the apex of infrequent, previously
unrecognized canalicular projections. Unique rapid fixation
techniques have identified these projections and have shown them
to be consistent with other studies suggesting that the adhesion
molecules are alphav beta3integrins. Our theoretical model predicts that the tensile forces acting on the integrins are <15 pN and thus
provide stable attachment for the range of physiological loadings.
The model also predicts that axial strains caused by the sliding of
actin microfilaments about the fixed integrin attachments are an
order of magnitude larger than the radial strains in the previously
proposed strain-amplification theory and two orders of magnitude
greater than whole-tissue strains. In vitro experiments indicated
that membrane strains of this order are large enough to open
stretch-activated cation channels.
|Subjects:||T Technology > TA Engineering (General). Civil engineering (General)
Q Science > QP Physiology
Q Science > QH Natural history > QH301 Biology
|Divisions:||University Structure - Pre August 2011 > School of Engineering Sciences > Bioengineering Sciences
|Date Deposited:||19 Mar 2008|
|Last Modified:||01 Jun 2011 04:43|
|Contact Email Address:||L.McNamara@soton.ac.uk|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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