Mechanical regulation of cell memory

Cell memory describes the capacity of a cell to retain induced biological changes following withdrawal of initiating signals. Accumulating evidence reveals that mechanical stimuli in the microenvironment not only drive immediate structural reorganization in cells and extracellular matrix (ECM), but also can induce long-term changes in cell phenotype and identity. These effects underlie critical biological phenomena, including cell migration, differentiation and reprogramming. In this Review, we present an integrative framework for understanding how mechanical signals modulate cellular structure, identity and function in the context of cell memory. We examine how external forces and the mechanical properties of the ECM reconfigure the structural memory of mechanosensitive molecules, spatial distribution of transcription factors and ECM organization. We offer insights on the mechanical regulation of epigenetic memory, highlighting both mechano-chemical pathways and direct mechanical influences on nuclear architecture.