STUDIES OF SINGLE CELL AND CELL POPULATION BEHAVIORS IN 3D CO-CULTURE MICROFLUIDIC SYSTEMS

Recent years have seen rapid expansion of the capabilities 
to recreate in vivo conditions using in vitro microfluidic assays.  
A wide range of single cell and cell population behaviors can now 
be replicated, controlled and imaged for detailed studies to gain 
new insights.  Such experiments also provide useful fodder for 
computational models, both in terms of estimating model parameters 
and for testing model-generated hypotheses.  Our experiments have 
focused in several different areas.  
1) Single cell migration experiments in 3D collagen gels have 
revealed that interstitial flow can lead to biased cell migration 
in the upstream direction, with important implications to cancer 
invasion.  We show this phenomenon to be a consequence of 
integrin-mediated mechanotransduction.  
2) Endothelial cells seeded in fibrin gels form perfusable 
vascular networks within 2-3 days through a process termed 
“vasculogenesis”.  The process by which cells sense their 
neighbours, extend projections and form anastomoses, and 
generate interconnected lumens can be observed through time-lapse 
microscopy.  
3) These vascular networks, once formed, can be perfused with 
medium containing cancer cells that become lodged in the 
smaller vessels and proceed to transmigrate across the endothelial 
barrier and invade into the surrounding matrix.  High resolution 
imaging of this process reveals a fascinating sequence of events 
involving interactions between a tumour cell, endothelial cells, 
and underlying matrix.  These three examples will be presented 
with a view toward gaining new insights through computational 
modelling of the associated phenomena.