Mechanical cues from the microenvironment can be efficiently transmitted to the nucleus to engage in the regulation of genome organization and gene expression. Recent technological and theoretical progress sheds new light on the relationships between cell mechanics, nuclear and chromosomal architecture and gene transcription.
Recent progress in the study of cellular mechanotransduction — the conversion of mechanical forces into biochemical signals — has increased our understanding of mechanobiology by providing novel insights into how mechanical inputs regulate cell behaviour and tissue homeostasis and how their deregulation might cause disease. This Focus issue includes Review articles and comments that discuss how mechanical forces are transduced into the cell, including into the nucleus, to control gene expression and to regulate morphogenesis, tissue regeneration and tumorigenesis. Also discussed is the therapeutic potential of modulating mechanotransduction with the use of synthetic matrices.
Physical cues regulate stem cell fate and function during embryonic development and in adult tissues. The biophysical and biochemical properties of the stem cell microenvironment can be precisely manipulated using synthetic niches, which provide key insights into how mechanical stimuli regulate stem cell function and can be used to maintain and guide stem cells for regenerative therapies.
The transcription factors YAP and TAZ have recently emerged as being conserved transducers of mechanical signals into cells and mediators of processes such as proliferation, migration and cell fate decision. The roles of YAP-mediated and TAZ-mediated mechanotransduction have now been documented in many physiological and pathological contexts, providing novel insights into cellular mechano-responses and their consequences.
Coordinated movements of cell collectives are important for morphogenesis, tissue regeneration and cancer cell dissemination. Recent studies, mainly using novelin vitroapproaches, have provided new insights into the mechanisms governing this multicellular coordination, highlighting the key role of the mechanosensitivity of adherens junctions and mechanical cell–cell coupling in collective cell behaviours.
Soon after their discovery in 2010, Piezo channels became a paradigm for studying mechanosensitive ion channels. These channels respond to physiologically relevant forces in diverse cellular contexts, and their dysfunction has been linked to various diseases. We are now starting to understand gating mechanisms of Piezo channels and their key roles in physiology.
News & Comment
Studies of mechanobiology lie at the interface of various scientific disciplines from biology to physics. Ulrich Schwarz discusses the importance of technological advances, quantification and modelling for the progress in understanding the role of forces in biology.
Christopher Chen highlights the early studies of mechanoregulation of cell–matrix adhesions that established mechanobiology as a cross-discplinary research field
Applying force to the nucleus reduces the diffusion barrier at nuclear pores and promotes nuclear import of certain proteins, including the transcription regulator YAP, depending on their molecular properties.