Microfabrication of 3D Microfluidic Environments for Osteocytes
Determine whether oscillating fluid flow applied to the osteocyte process alone is sufficient to elicit the response observed in parallel plate monolayers. Completion of this project will result in specific knowledge of how intracellular forces due to loading-induced fluid flow are transmitted by structural proteins and details of how forces on those proteins activate intracellular signaling cascades leading to regulation of downstream osteogenic behavior. By uncovering details of the molecular switch responsible for cellular transduction of mechanical loading, this project will lead to novel targets for pharmacological intervention in a variety of bone diseases.
We will employ a 3D microfabricated flow system that incorporates large voids for osteocytes and narrow tunnels which support cell process ingrowth. A microfluidics approach will allow flow delivery to the processes alone. Intracellular calcium levels will be monitored on a single cell basis to determine responsiveness.