MechSE professor Ning Wang’s article “Effects of forces on chromatin” was featured in APL Bioengineering, a journal of the American Institute of Physics.
“Mechanical forces are known to profoundly influence living cells, tissues, and organisms,” Wang said. “However, the underlying mechanisms of mechanotransduction (converting mechanical signals into biochemical processes and biological responses) are not well understood.”
This article discusses recent discoveries from the Wang Lab and colleagues that forces can directly stretch the chromatin (the packed DNA and genome in the cell nucleus) to rapidly activate multiple genes simultaneously and thus act as a “super transcription factor,” highlighting the potential of force and mechanics in mechanomedicine, an emerging field of mechanobiology-based medicine, to diagnose, treat, and cure various complex diseases.
Wang is the Leonard C. and Mary Lou Hoeft Endowed Professor in Engineering. He joined the MechSE faculty in 2006. Previously, he was a faculty member in the Department of Physiology and Cell Biology in the Harvard School of Public Health.
The article’s abstract is below. The full article is available on the AIP website.
Chromatin is a unique structure of DNA and histone proteins in the cell nucleus and the site of dynamic regulation of gene expression. Soluble factors are known to affect the chromatin structure and function via activating or inhibiting specific transcription factors. Forces on chromatin come from exogenous stresses on the cell surface and/or endogenous stresses, which are regulated by substrate mechanics, geometry, and topology. Forces on chromatin involve direct (via adhesion molecules, cytoskeleton, and the linker of nucleoskeleton and cytoskeleton complexes) and indirect (via diffusion and/or translocation processes) signaling pathways to modulate levels of chromatin folding and deformation to regulate transcription, which is controlled by histone modifications and depends on magnitude, direction, rate/frequency, duration, and modes of stresses. The rapid force transmission pathway activates multiple genes simultaneously, and the force may act like a “supertranscription factor.” The indirect mechanotransduction pathways and the rapid force transmission pathway together exert sustained impacts on the chromatin, the nucleus, and cell functions.