Abstract
Three-dimensional (3D) cell migrations are regulated by force interactions between cells and a 3D extracellular matrix (ECM). Mapping the 3D traction force generated by cells on the surrounding ECM with controlled confinement and contact area will be useful in understanding cell migration. In this study, double-sided micropost arrays were fabricated. The cell traction force was mapped by microposts on the top and bottom of opposing surfaces with a controlled separating distance to create different confinements. The density of micropost arrays was modified to investigate the effect of cell contact area on 3D traction force development. Using MC3T3-E1 osteoblastic cells, the leading traction force was found to increase with additional contact surface on the top. Summing force vectors on both surfaces, a large force imbalance was found from the leading to trailing regions for fast migrating cells. With 10 μm separation and densely arranged microposts, the traction force on the top surface was the largest at 28.6 ± 2.5 nN with the highest migration speed of 0.61 ± 0.07 μm min−1. Decreasing the density of the top micropost arrays resulted in a reduced traction force on the top and lower migration speed. With 15 μm separation, the cell traction force on the top and migration speed further decreased simultaneously. These results revealed traction force development on 3D ECM with varied degrees of confinement and contact area, which is important in regulating 3D cell migration.
Highlights
Cell migration studies inside three dimensional (3D) microenvironment are important because cells in vivo are surrounded by other cells and an extracellular matrix (ECM).[1,2,3,4] The ECM in vivo is not a homogenous meshwork
Vertical con nement is one of the basic models where cells migrate in between two opposite layers in vivo, such as the space between two peritoneal layers covering the inner organs, bone cavities covered by monolayers of osteoblastic cells, and perivascular space between the pia mater and elastic membrane covering the smooth muscle cells inside brain vessels.[5,55]
Cell migration was found to be regulated by cell contact with 3D ECM and cell traction force on adhesive sites.[13]
Summary
Cell migration studies inside three dimensional (3D) microenvironment are important because cells in vivo are surrounded by other cells and an extracellular matrix (ECM).[1,2,3,4] The ECM in vivo is not a homogenous meshwork.
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