From the membrane to the nucleus: Mechanical signals and transcription regulation

Abstract

Mechanical forces drive and modulate a wide variety of processes in eukaryotic cells including those occurring in the nucleus. Relevantly, forces are fundamental during development since they guide lineage specifications of embryonic stem cells. A sophisticated macromolecular machinery transduces mechanical stimuli received at the cell surface into a biochemical output; a key component in this mechanical communication is the cytoskeleton, a complex network of biofilaments in constant remodeling that links the cell membrane to the nuclear envelope. Recent evidence highlights that forces transmitted through the cytoskeleton directly affect the organization of chromatin and the accessibility of transcription-related molecules to their targets in the DNA. Consequently, mechanical forces can directly modulate transcription and change gene expression programs. Here, we will revise the biophysical toolbox involved in the mechanical communication with the cell nucleus and discuss how mechanical forces impact on the organization of this organelle and more specifically, on transcription. We will also discuss how live-cell fluorescence imaging is producing exquisite information to understand the mechanical response of cells and to quantify the landscape of interactions of transcription factors with chromatin in embryonic stem cells. These studies are building new biophysical insights that could be fundamental to achieve the goal of manipulating forces to guide cell differentiation in culture systems.