In Situ Observation of Compressive Forces Experienced by DNA Loci in the Nucleus of Living HeLa Cell

We are interested in how the production, sensing, and transduction of mechanical forces at the molecular level relate to the global mechanics of chromosomes. To answer this question, we are developing new approaches to quantify and visualize intracellular forces with nanoscale precision, over micron-scale distances, and in their physiological context. Our work aims to apply nanotechnologies to measure forces acting within and among chromosomes, with a focus on chromosome-wide mechanical patterning and its contributions to genome function.



In this talk, I will discuss DNA origami-based nanosensor, which enable quantitative luminescent imaging of mechanical effects in situ. The sensor represents a dynamic DNA nanostructure, which changes the color of photoluminescence in response to the applied force. This probe can register compressive mechanical deformations on the scale just above the thermal bath (1.6 kT or 0.23-0.36±0.01 pN applied over ~18 nm). When attached to the chromosomes, these sensors report an (F,x,y,z,t) map of intracellular forces. I will discuss the application of the sensors to detect patterns of forces experienced by multiple DNA loci in the interphase nucleus of living HeLa cell.