UCLA Samueli Newsroom
AUCLA-led research team has discovered that the viscoelasticity of a cell’s surroundings — the property that allows them to harden and soften as they deform and relax under stress over time — can influence how the cell’s genetic material is organized and accessed.
The study, published in Nature Communications, shows that viscoelastic materials influence gene expression, opening new paths for using engineered materials to more effectively convert cells into other types, such as neurons or stem cells. The findings point to broad potential in regenerative medicine, disease research and therapeutic development.
“The biological tissues that surround cells deform under stress and then gradually relax, or ‘flow,’ back to their original state over time, rather than instantly snapping back like a rubber band,” said study leader Song Li, a chancellor’s professor of bioengineering at the UCLA Samueli School of Engineering. “We found that softer, more viscoelastic materials make cells more adaptable by loosening their DNA structure and enhancing gene activity linked to reprogramming.”
Previous research linked matrix stiffness to changes in cell structure and function. This study goes further, showing that viscoelasticity plays a crucial role in modulating the epigenome, the system that regulates gene expression.
To test their hypothesis, the researchers engineered a series of biological tissue-like materials with variable viscoelastic properties, allowing the team to control when the materials stiffened and relaxed. They then examined how changes in these properties affected cellular behavior and epigenetic regulation.
“One of the most striking observations in our study was that the effects of matrix viscoelasticity depended strongly on stiffness,” Li said. “We found that matrix viscoelasticity significantly influenced nuclear structure, chromatin organization and gene expression, but only when the matrix was soft.” At UCLA, Li also holds a joint appointment with the David Geffen School of Medicine and is a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and the Jonsson Comprehensive Cancer Center.
Yifan Wu, a recent UCLA Samueli doctoral graduate from Li’s group, is the study’s lead author. Additional authors include Yang Song, Jennifer Soto, Tyler Hoffman, Xiao Lin, Aaron Zhang, Ramzi Massad, Siyu Chen, Xiao Han and Kun-Wei “James” Yeh — all members of Li’s research group. Senior authors are Luo Gu, an assistant professor of materials science and engineering at Johns Hopkins University; Amy Rowat, a professor of integrative biology and physiology and bioengineering at UCLA; and Zhen Gu, an adjunct professor of bioengineering at UCLA and a professor at Zhejiang University, China.
Xiao Han from Zhen Gu’s iMedication Lab, Dongping Qi from Rowat’s research group, as well as Zhiwei Fang and Joon Eoh from Luo Gu’s group are also authors on the paper.
The research was funded by the National Institutes of Health, the National Science Foundation, the Department of Defense and the UCLA Broad Stem Cell Research Center.