You may have thought that the cells in your body are stationary, sitting in fixed locations and forming the tissues and organs of your body. Research has shown however that the cells within the body actually do a lot of moving. Cells move for a variety of reasons - during wound healing when healthy cells around a damaged area move to cover up the wound, or in diseases such as cancer where cancerous cells spread from organ to organ.
Till now, it was thought that only a few factors like chemical signals and mechanical forces play a role in regulating cell movement. A team of researchers working at the Indian Institute of Science, Bangalore, has discovered how position cues can also influence the speed and the direction of movement of cells. The research team, led by Dr. Namrata Gundiah from the Department of Mechanical Engineering have also figured out a possible mechanism by which the force to move the cells is generated.
The team wanted to see if the position of cells within a specific shape affected the way the cells spread on a flat surface. To answer this question, the team grew a single layer of cells within stencils of different shapes - circle, square or cross (plus symbol). They then removed the stencil constraints, freeing the cells to move in any direction they like.
As it turns out, the position of cells within a shape influences the velocity and the distance to which they move. Cells located on the edges move faster than those located in the interior! They also observed that cells located on straight edges or in regions that curved inwards (concave surfaces) and those located on regions that curved outwards (convex surfaces) moved faster than cells on very pointed curves, such vertices of the cross. Interestingly, all the cells on the very edge don’t even move at the same speed! The team identified leader cells that are evenly spaced at a distance of around 125µm along the straight edges, which forge ahead of the rest. “While several studies have predicted the distance at which two successive leader cells arise along the leading edge, this study provides early experimental values for the distance between two adjacent leader cells” says Ankur Hemant Kulkarni, a PhD student who was part of the project. The cells don’t move at the same rate over a period of time. In fact their speed follows three phases after the stencil patterns are removed – it first increases, then remains constant in the second phase and then slows down in the third phase. The direction of movement of the cells also depends on the location. In the square and the circle, the cells tended to move outwards, perpendicular to the edge of the boundary. But something different happened at the intersection of the cross. While cells from the center of the cross moved diagonally outwards, cells at the pointed ends of the cross moved very little in comparison.
But how is all the force that the cells need to move, generated? The answer lies in the cables of proteins called actin and myosin that form in the cells located on the leading edge of the shape. Actin is a protein that can polymerize to form long filaments. When these filaments contract, they generate a force that can pull the part of the cell that they are attached to. For an expanding sheet of cells, this skeleton of actin and myosin filaments serve to pull the cells outward.
The scientists found that the actomyosin cable was absent in cancer cells (MCF7), but present in non-cancerous cells called MDCK cells. When the researchers disturbed the actin and myosin bands, in the MDCK cells they found that the velocities of the cells decreased dramatically. They found that the presence of this protein cable is essential in the creation of leader cells in the “normal” MDCK cell clusters.
The scientists hypothesize that the cells at the sharp ends of a shape, such as the vertices of the cross, experience a greater tension compared to the cells in other region and therefore mover shorter distances. On the other hand, the emergence of leader cells along straight edges pull the remaining cells outward, causing them to travel over longer distances.
This study demonstrates the importance of the actomyosin cables in the migration of cells. This shows the differential migration patterns in the two kinds of cells. Current investigations in Dr Gundiah’s lab are modeling these interactions between cells to explore the importance of cables and curvature in creation of leader cells which determine the migration direction of cells. These findings have implications in tissue engineering, the science of growing tissues and organs in laboratory conditions. They also help improve our understanding of the spread of cancers within the body.
About the Author:
Dr Namrata Gundiah is an Associate Professor at the Department of Mechanical Engineering, Indian Institute of Science, Bangalore.
About the Paper
The paper ‘Advancing Edge Speeds of Epithelial Monolayers Depend on Their Initial Confining Geometry’ was published in the journal PLoS ONE in 2016.