What makes a stem cell stiff or squishy?

Mesenchymal stem cells (MSCs) are a type of connective tissue stem cell with the ability to differentiate into a variety of cell types. While this versatility could be useful for future regenerative medicine, the factors that cause the cells to change from one type to another aren’t well understood.

Panepinto Zayati et al. studied the mechanical properties that affect differentiation in MSCs to contribute to understanding these causes.

“In recent years, it has become clear that MSCs do not respond only to chemical signals,” said author Carmen Panepinto Zayati. “They are also highly sensitive to physical cues: the stiffness of their environment, the forces applied to them, and the way they deform under stress.”

Using atomic force microscopy to measure how cells respond to mechanical stimulus, the researchers calculated the Young’s modulus of MSCs and their poroelastic diffusion constant — or, how much the cells resist deformation and how they relax after being deformed.

The researchers found that these two measurements differed between MSC donor lines, a consequential result for future studies. Additionally, they observed that female-derived cells were stiffer than male-derived cells, but there wasn’t a significant difference in their poroelastic behavior.

“This points to a possible divergence between structural and fluid-related mechanical properties, suggesting that different aspects of cell mechanics may be regulated by distinct biological mechanisms,” Panepinto Zayati said.

Panepinto Zayati hopes that the data from this study will be used as a reference point for further experimental design.

“This study is designed as a starting point: a controlled framework to begin quantifying mechanical variability in MSCs,” Panepinto Zayati said. “Ultimately, the end goal could be the use of this growing body of data to develop predictive models of cell behavior.”

Source: “Exploring the mechanical heterogeneity of human adipose-derived mesenchymal stem cells: A pilot study,” by Carmen Panepinto Zayati, Andrea Lagomarsino, Juliana Redondo, Alessia Bacci, Sajedeh Kerdegari, Claudio Canale, and Leonardo Ricotti, Biophysics Reviews (2026). The article can be accessed at https://doi.org/10.1063/5.0323081 .