Strain amplification and integrin based signaling in osteocytes

Abstract

Recent morphological studies have suggested that osteocyte processes are directly attached at discrete locations along the canalicular wall by beta3 integrins at the apex of infrequent, previously unrecognized, canalicular projections. This discovery has led to a new paradigm for the initiation of intracellular signaling, which provides a possible long sought after molecular mechanism for the initiation of intracellular signaling in bone cells. The quantitative feasibility of this hypothesis is explored with a detailed theoretical model, which predicts that axial strains due to the sliding of actin microfilaments about the fixed integrin attachments are in 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.

Figure 1

A) Transverse (bar=500nm) and B) longitudinal (bar=100nm) cross-section of TEM images showing canalicular projections coming into direct contact with the cell process and transverse tethering elements spanning the majority of the pericellular space between the cell process and canalicular wall.

Figure 2

A) Transverse and B) longitudinal cross-section of the idealized structural model showing the direct attachment of an osteocyte process to a local canalicular projection via integrins. (Solid line – undeformed; dashed line – deformed process and tethering elements).

Figure 3

A) The radial strain ε_r for a tissue loading of 10 MPa is shown for comparison), and B) the axial strain ε_a as a function of loading frequency with tissue loading amplitude as a parameter.