Cell growth under geometrical constraints
The 3D MULTICELL GROWTH (How mechanical forces regulate tissue growth in defined 3D geometries) project has successfully developed a quantitative in vitro tissue growth assay. Integrated with bioengineering techniques, the team tested if mechanical forces were translated into cell behaviour at the microscopic level by quantifying tissue growth processes in millimetre-sized scaffold pores. Using fluorescence resonance energy transfer on the extracellular matrix protein fibronectin, the researchers measured how the mechanical stretching of those extracellular fibers changed during tissue growth, and force fluctuations were also measured using fluorescent marker particles. Overall, results show that proliferation of fibroblasts that produced the extracellular matrix is significantly increased near the surface of growing tissues, while cells deeper in the more matured 3D tissue are switched to being mostly quiescent. We analysed mechanisms that regulate such tissue maturation processes using well controlled microtissues. Particular attention was thereby placed on investigating the role of mechanical forces and extracellular matrix. Regenerative therapies and tissue engineering often involve the use of scaffolds as guiding structures for tissue repair and regrowth. By revealing how cell forces and matrix properties impact biological growth in such geometrically defined environments, this study opens up new possibilities to improve the outcome of wound healing processes by targeting mechanobiological pathways. The tests developed by 3D MULTICELL GROWTH could also be adapted for other cell types.
