The environment that surrounds cells in a tissue or organ, the extracellular matrix, is arguably just as critical to cell function as the cell itself. Researchers from the University of Illinois at Urbana-Champaign have now devised a lab-based method to alter the stiffness of this surrounding architecture, and have shown that softer environments increase the functional properties of vascular cells (Biomaterials 140 45). They also found that applying a mechanical force to the cells – designed to mimic the effect of blood flow over vascular cells – increased functionality in cells with stiffer surrounding environments, which are typically associated with aged or diseased vascular systems.
Deborah Leckband and her team showed that a combination of extracellular stiffness and mechanical force disrupts the vascular system, which then initiates a remodelling of the intracellular architecture. They assessed the functionality of vascular cells by measuring the distance between specialized proteins that sense changes in the physical environment surrounding cells, and then translate them into signals that alter cell function. The researchers found that disturbing the receptors of these so-called gap-junction proteins with a mechanical force had a negative biophysical effect on the cells, confirming that both mechanical and physical properties surrounding a cell affect its functionality.
The team used special biomaterials called hydrogels to alter the stiffness of the extracellular matrix surrounding vascular cells. Hydrogels offer extremely useful properties, since they have the structural properties of a solid but can also attain a water saturation of more than 99%. By altering the concentration of the primary material within the hydrogel, the researchers were able to vary the stiffness of the surrounding environment between 1.1 kPa and 1 GPa.
In these experiments, the cells were placed on top of a hydrogel, but other researchers have encapsulated cells within a hydrogel to provide a 3D environment. In future, this approach could also be used by the Illinois group, and it can also be applied to many different types of cells, not just to vascular cells.
With this new research, Leckband and her team have provided a better understanding of how the biophysical properties surrounding vascular cells affect their function. By probing the effect of increased stiffness on vascular cells, they have shown how cell function can be disturbed by the stiffening of the vascular architecture that’s observed with age. The results could also lead to improved strategies for modelling disease, since in vitro models could replicate vascular diseases more effectively by using stiff hydrogels to mimic aged and diseased vascular environments.