Adding or removing water from a stem cell can change the destiny of the cell, researchers have discovered in a new study published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) journal.

The research found that altering the volume of a cell changed its internal dynamics, including the rigidness of the matrix lining the outer surface. In stem cells, removing water condenses the cell, influencing the stem cells to become stiff pre-bone cells, while adding water causes the cells to swell, forming soft pre-fat cells.

Researchers have long understood that stem cells are influenced by the cells around them, picking up cues on what their function should be based on the stiffness of the matrices of neighboring cells.

The results, however, confirm that nature plays as much of a role as nurture in stem cell behavior and development.

“The findings from this study add a fascinating new tool to our understanding and utilization of stem cell biology for regenerative medicine,” said Praveen Arany, DDS, PhD, co-author and assistant professor in the Department of Oral Biology in the University at Buffalo School of Dental Medicine.

The study was led by Ming Guo, PhD, d’Arbeloff Assistant Professor in the Department of Mechanical Engineering at the Massachusetts Institute of Technology; and David Weitz, PhD, Mallinckrodt Professor of Physics and of Applied Physics in the John A. Paulson School of Engineering and Applied Sciences at Harvard University.

“For the first time, we’re beginning to understand the importance of cell volume and cellular water content in the mechanical properties and physiological functions of cells,” said Guo, who began the research as a graduate student in Weitz’s lab at Harvard.

The research originally sought to understand the effects of volume on a cell’s characteristics and functions. Cell volume is highly regulated and changes frequently over the course of a cell’s life, increasing as the cell grows and decreasing when it divides.

These changes in volume are a result of variations in the amount of protein, DNA and other materials within the cell, though they mostly remain constant. But cells can also experience rapid and extreme changes in size and density through the absorption or release of water, spreading or shrinking in as little as 20 minutes.

By increasing or decreasing the volume of cells by 20 percent, the investigators found that the cells experienced several internal changes, including in gene expression and stiffness.

Knowing the role cell stiffness plays in the development of stem cells, the researchers began to wonder if cell volume could affect their fate as well.

To test the premise, investigators placed stem cells at their normal volume in a hardened hydrogel substrate to simulate the rigidness of bone cells. After one week, a large portion of the stem cells developed into pre-bone cells.

The experiment was repeated with a softened hydrogel substrate. In the softer environment, there was a significant decrease in the number of stem cells that became pre-bone cells. However, when water was removed from the cells to decrease their volume by 20 percent, the number of stem cells that became pre-bone cells increased, despite being in the softer substrate.

A similar experiment was conducted using glass. Researchers placed stem cells on glass to simulate a stiffer environment and found that few of the cells developed into pre-fat cells. It was not until the volume of the stem cells was increased by 20 percent that a spike in the formation of fat cells was found.

The investigators discovered that changing the volume of the cells caused them to behave similarly to as if they were under environmental pressures.

“The surprising thing about these experiments is the observation that volume seems to be related to so much about the cell