Crowding causes cells to produce an orderly matrix of molecules

When researchers conduct experiments on the way cells grow and respond to outside cues, they tend to use solutions that are much more dilute than the crowded environments found inside living cells. Now, new research from MIT shows that this dilute environment may skew the results of such experiments.

Using a technique that more closely mimics the crowded environment in actual cells, researchers found that certain molecules ''organise more like we would expect they would in the body,'' says Krystyn Van Vliet, the Paul M Cook Career Development Associate Professor of Materials Science and Engineering at MIT. The research is described this week in the journal PLoS ONE, in a paper co-authored by Van Vliet.

''The cell in the body lives in a very crowded environment,'' Van Vliet says. Most researchers have done their work with dilute solutions, which are easier to control and analyse, but have not fully recognised how this may affect the outcomes. It turns out that producing a more crowded environment ''induces dramatic alignment of the protein networks outside the cell,'' which in turn causes the cell to align its internal structure, she says.

Research approximating ''what really happens in the crowded environments'' surrounding living cells is virtually ''untouched territory,'' says Adam Zeiger, an MIT graduate student in materials science and engineering and lead author of the new paper. The research was conducted under the Singapore-MIT Alliance in Research and Technology (SMART), and included SMART postdoc Felicia Loe and professor Michael Raghunath at the National University of Singapore, as well as biological engineering graduate student Ran Li at MIT.

Cells manufacture a matrix that controls the structure of their internal environment, says Van Vliet, who also has an appointment in the Department of Biological Engineering at MIT. ''The matrix serves as a template,'' she says, sending signaling cues to the cells on how to behave and organise their internal structure. When the matrix-making molecules are studied in vitro in a laboratory environment, they produce disorganised networks, rather than the precisely organised matrices they create in living organisms.

But, now, by simply introducing tiny particles - which they call ''crowders'' - into a lab solution, ''we can create the same effect'' Zeiger says, causing matrix fibers to align themselves. Using crowders synthesised by Raghunath and Loe, the experiments were carried out on adult stem cells, and the protein that formed the matrix was made of collagen and fibronectin, structural materials that the body uses for connective tissue and skin.