Solid tumors possess an abundance of genetic changes, much moreso than ‚Äòliquid‚Äô tumors or tumors in soft tissues, and similar trends are evident even in normal tissues. Here, we use gene editing to visualize and track sequence-specific changes to a cell‚Äôs DNA, as confirmed by single cell sequencing. We see that heritable changes are more frequent under the mechanical stresses of confinement intrinsic to stiff, solid tissues and tumors. Although such stresses can be toxic, changes in chromosome copy number in viable cells not only affect gene expression from affected chromosomes but can also impact phenotype, including motility and proliferation. The approach is applied to cancer cells as well as normal, pluripotent stem cells and is further tested in vivo. Genetic changes scale more strongly with cell divisions under stressed versus unstressed conditions, and mechanisms of genetic change involve stress-dependent symmetry breaking with insights from liquid crystal defects. Ultimately, mechanotransduction extends to mechano-genetic variation.

Heritable changes to a cell’s DNA sequence under mechanical stress

The Virtual Technical Meeting of the Society of Engineering Science 2020 is the first fully virtual meeting of the SES community to envision and connect during the hiatus created by Covid-19, providing a platform for the exchange of ideas, and to showcase the latest research in the field of engineering science.

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