This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Cells in our bodies squeeze through dense tissue channels, thread past neighboring cells and navigate every nook and cranny within the extracellular matrix—the mesh-like network that surrounds and supports cells. How well they do this can shape a wide range of physiological processes, from wound repair to the spread of cancer.
A team led by Assistant Professor Andrew Holle from the Department of Biomedical Engineering at the College of Design and Engineering, National University of Singapore (NUS CDE) has shown that cells can carry a physical memory of the environments they have experienced and that this memory can influence how efficiently they later move through confined spaces. Crucially, the team identified NFATC2, a member of the NFAT family of transcription factors, as a key regulator of this process. A transcription factor is a protein that helps control which genes are switched on or off.
By linking a cell's past mechanical environment to changes in gene activity, NFATC2 appears to help encode and maintain this "mechanical memory"—a finding that could help researchers better understand how cells migrate during cancer metastasis, wound healing and tissue regeneration and inform the design of biomaterials that guide cell behavior. The study focuses on a question at the core of mechanobiology: How do cells respond to the physical properties of their surroundings? Cells are known to sense whether their environment is soft or stiff.
A cell in soft tissue, for example, can behave differently from one on a rigid surface. What has been less clear is whether those physical experiences persist after a cell moves elsewhere and whether they affect later behavior. "Cells are usually studied based on where they are at a given moment, but our findings show that where they have been is also important," Holle said.
"A cell's physical history can shape how it responds to a new challenge. That gives us another way to think about migration. We can think about it as behavior influenced by both present conditions and past mechanical experience." To test this, the researchers grew three types of cells on materials of different stiffness: healthy fibroblasts, fibrosarcoma cells and highly invasive breast cancer cells.
The cells were first "primed" for several days on soft or stiff hydrogels, then transferred to a common surface or into microchannel devices that mimic the tight spaces cells encounter in tissues. The team found that fibroblasts and fibrosarcoma cells that had been primed on soft substrates moved more efficiently through very narrow channels than cells primed on stiffer materials. In some confined settings, soft-primed cells migrated more than 60% faster than stiff-primed cells.
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