Dynamic self-reinforcement of gene expression determines acquisition of cellular mechanical memory

Christopher C. Price, Jairaj Mathur, Joel D. Boerckel, Amit Pathak, Vivek B. Shenoy

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Mechanotransduction describes activation of gene expression by changes in the cell's physical microenvironment. Recent experiments show that mechanotransduction can lead to long-term “mechanical memory,” in which cells cultured on stiff substrates for sufficient time (priming phase) maintain altered phenotype after switching to soft substrates (dissipation phase) as compared to unprimed controls. The timescale of memory acquisition and retention is orders of magnitude larger than the timescale of mechanosensitive cellular signaling, and memory retention time changes continuously with priming time. We develop a model that captures these features by accounting for positive reinforcement in mechanical signaling. The sensitivity of reinforcement represents the dynamic transcriptional state of the cell composed of protein lifetimes and three-dimensional chromatin organization. Our model provides a single framework connecting microenvironment mechanical history to cellular outcomes ranging from no memory to terminal differentiation. Predicting cellular memory of environmental changes can help engineer cellular dynamics through changes in culture environments.

Original languageEnglish
Pages (from-to)5074-5089
Number of pages16
JournalBiophysical Journal
Volume120
Issue number22
DOIs
StatePublished - Nov 16 2021

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