Mechanically primed cells transfer memory to fibrous matrices for invasion across environments of distinct stiffness and dimensionality

José A. Almeida, Jairaj Mathur, Ye Lim Lee, Bapi Sarker, Amit Pathak

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Cells sense and migrate across mechanically dissimilar environments throughout development and disease progression. However, it remains unclear whether mechanical memory of past environments empowers cells to navigate new, three-dimensional extracellular matrices. Here, we show that cells previously primed on stiff, compared with soft, matrices generate a higher level of forces to remodel collagen fibers and promote invasion. This priming advantage persists in dense or stiffened collagen. We explain this memory-dependent, cross-environment cell invasion through a lattice-based model wherein stiff-primed cellular forces remodel collagen and minimize energy required for future cell invasion. According to our model, cells transfer their mechanical memory to the matrix via collagen alignment and tension, and this remodeled matrix informs future cell invasion. Thus, memory-laden cells overcome mechanosensing of softer or challenging future environments via a cell–matrix transfer of memory. Consistent with model predictions, depletion of yes-associated protein destabilizes the cellular memory required for collagen remodeling before invasion. We release tension in collagen fibers via laser ablation and disable fiber remodeling by lysyl-oxidase inhibition, both of which disrupt cell-to-matrix transfer of memory and hamper cross-environment invasion. These results have implications for cancer, fibrosis, and aging, where a potential cell-to-matrix transfer of mechanical memory of cells may generate a prolonged cellular response.

Original languageEnglish
Article numberar54
JournalMolecular biology of the cell
Issue number6
StatePublished - May 1 2023


Dive into the research topics of 'Mechanically primed cells transfer memory to fibrous matrices for invasion across environments of distinct stiffness and dimensionality'. Together they form a unique fingerprint.

Cite this