The Shape of Things
A group led by Milan Mrksich and including post-doctoral researcher Kris Killian at the University of Chicago recently published a cool new finding on the behavior of mesenchymal stem cells (MSCs). Mesenchymal stem cells are of interest to biologists because they are pluripotent, that is, they can become several different types of cells depending on their environment. MSCs come from bone marrow and can become bone cells (osteoblasts), cartilage cells (chondrocytes) or fat cells (adipocytes) in a process called differentiation.
Before the Mrksich group started their work, the thought was that the main influence on stem cell differentiation was the chemical signals surrounding the cells. Given one group of signals, cells would go down one developmental path, and given another set they would take a different path. The Mrksich group found that the shape of the cell was a greater influence on MSC differentiation than chemical signals. Most of the time MSCs are shaped kind of like fried eggs. They have a big, spherical nucleus rising up out of a broad, flat plain of cytoplasm, literally the goo that makes up the rest of the cell. How did the Mrksich lab change the shape of the cell? By giving them a specific pattern to fit into. MCS cells like to grow on certain surfaces and not on others. By coating only parts of glass microscope coverslips with the surface material required by the cells, the Mrksich lab was able to create different shapes for the MSCs to grow on. When the cells were grown on curvy shapes, such as circles or flowers (think cherry blossoms) they grew into fat cells (adipocytes) and when the cells were grown on more angular shapes, like holly leaves or stars, they grew into bone precursor cells (osteoblasts). This happened regardless of the chemical signals the cells received, and even when the cells were given two competing chemical signals. The shape played the dominant role in determining the cell’s fate.
The group also showed that the cytoskeleton plays a major roll in the influence of shape on differentiation. The cytoskeleton is literally “cell skeleton,” it’s the internal scaffolding proteins that allow a cell to keep its shape, move and transport things around the cell. The group thinks that cell fate is influenced by cell contractility (you can think of this like stretchy-ness, I guess is a good way to describe it). The curvy shapes lead to more “relaxed” cells, and those cells tend to differentiate into fat cells, and the angular shapes lead to more “rigid” cells, which tend toward becoming bone cells.
The original paper can be found in the March 1 early edition of the Proceedings of the National Academy of Sciences (PNAS). It contains some beautiful images of the cells on their shape templates, so it’s worth a look just for those.