Natalie Ahn, Kristi Anseth, and Sangeeta Bhatia are learning that physical forces and chemical signals from its neighbors make a cell behave more like a cell.

In the body, cells are accustomed to living large, in three dimensions, embedded within an extracellular matrix (ECM). Through the pores of the fibrous ECM, a cell is bathed in nutrients and signaling molecules. A thin basement membrane anchors the cell to surrounding connective tissues and emits chemical signals that regulate some cell processes. In addition, physical forces push and pull the cell from all directions.

Without this extracellular community, cells grown in single layers on standard flat cultures will proliferate, but they usually don’t differentiate into specialized cells forming structures such as capillaries. They can be inadequate models yielding misleading results. For example, researchers testing drugs against cancer cells in 2-D cultures may overestimate their potency, because the cells are more vulnerable to being killed.

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So scientists in a wide range of fields are turning to more complex and realistic three-dimensional (3-D) culture methods to provide cells with a more familiar home away from home. Generally, these microenvironments are gel-like materials with components of the basement membrane and the ECM.

The differences are spectacular. Now, cells are being coaxed to form blood vessels or potential implantable repair tissues, including miniature livers and other organs; they can form tiny spheres that mimic breast tissue for use in breast cancer research; and the methods are showing great promise for stem cell research.

Photos: Ahn: Carmel Zucker, Anseth: Carmel Zucker, Bhatia: Jason Grow

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