Mar 24, 2020

Mechanical memory in cells emerges from mechanotransduction with transcriptional feedback and epigenetic plasticity

BioRxiv : the Preprint Server for Biology
J. MathurAmit Pathak

Abstract

Emerging evidence shows that cells are able to sense and store a memory of their past mechanical environment. Since existing mechanotransduction models are based on adhesion and cytoskeletal dynamics that occurs over seconds and minutes, they do not capture memory observed over days or weeks. We postulate that transcriptional activity and epigenetic plasticity, upstream of adhesion-based signaling, need to be invoked to explain long-term mechanical memory. Here, we present a theory for mechanical memory in cells governed by three key components. First, cells on a stiff matrix are primed by a transcriptional reinforcement of cytoskeletal signaling. Second, longer stiff-priming progressively produces more memory-regulating factors and reduces epigenetic plasticity. Third, when stiff-primed cells move to soft matrix, the reduced epigenetic plasticity blocks new transcription required for cellular adaptation to the new matrix. This stalled transcriptional state gives rise to memory. We validate this model against previous experimental findings of memory storage and decay in epithelial cells migration and stem cell differentiation. We also predict wide-ranging memory responses for cells with varying protein kinetics and priming dura...Continue Reading

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Mentioned in this Paper

Genome
Trees (plant)
Research Methodology
Nucleic Acid Sequencing
Phylogenetic Analysis
Site
Sequencing
Massively-Parallel Sequencing
Chromosomes
Analysis

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