Mechanical memory helps explain how cells adapt their movement to changing environments

Cells within our bodies navigate complex environments, from traversing dense tissue channels to threading between neighboring cells. This ability to move efficiently can impact various physiological processes, such as wound healing and cancer progression. Researchers from the National University of Singapore (NUS) have discovered that cells can retain a physical memory of their past environments, which can influence their movement in confined spaces.

The study, led by Assistant Professor Andrew Holle, identified a transcription factor called NFATC2 as a crucial regulator of this mechanical memory. Transcription factors regulate which genes are turned on or off, allowing cells to encode and maintain their mechanical history. By linking a cell's past mechanical environment to changes in gene activity, NFATC2 helps encode and maintain this memory.

The researchers observed that cells primed on soft substrates moved more efficiently through narrow channels than cells primed on stiffer materials. This suggests that cells retain a memory of their past mechanical experiences, even after being transferred to new environments. However, the invasive breast cancer cells did not retain the same stiffness-dependent behavior after being moved, indicating that different cell types may use distinct strategies to adapt to changing surroundings.

The study focused on understanding how cells respond to the physical properties of their surroundings. While cells can sense whether their environment is soft or stiff, the researchers found that the physical experiences persist after a cell moves elsewhere and affect later behavior. This discovery could help researchers better understand how cells migrate during cancer metastasis, wound healing, and tissue regeneration.

It may also inform the design of biomaterials that guide cell behavior, as understanding mechanical memory could help predict how cells behave after leaving one environment for another. The team used RNA sequencing to examine gene activity after mechanical priming and identified NFATC2 as a key player in this process. When NFATC2 activity was disrupted, the migration advantage seen in soft-primed cells disappeared, highlighting the link between mechanical memory and gene regulation.

Further research is needed to determine how these findings extend to different tissues and disease states. The researchers plan to investigate whether confinement itself can leave a lasting mechanical imprint on cells, such as changes in nuclear shape, cytoskeletal organization, or chromatin state.