Chromosomes are commonly viewed as being crowded and entangled within the nucleus, with chromatin often thought to be a gel-like material during interphase. However, due to limited methods for making direct mechanical measurements within the nuclei of living cells, many of the physical properties of chromosomes in their natural state have remained a mystery. Now, researchers from the French National Centre for Scientific Research (CRNS), the Curie Institute and Sorbonne University have for the first time measured the response of a chromosome to external forces in a living cell, revealing that interphase chromatin has liquid-like properties.
The researchers achieved this novel micromanipulation of chromosomes within live cells by attaching GFP-ferritin magnetic nanoparticles to specific genomic loci and applying magnetic forces through magnetic microarrays. The loci were injected with the magnetic nanoparticles using microinjection procedures optimized for cell survival and a custom widefield epifluorescence microscope was used to capture time-lapse images as the magnetic forces were applied. The team generated force maps to estimate the forces applied to the genomic loci and were able to use this information and the timelapse images to analyze the chromosomes’ physical properties.
The team observed viscoelastic displacements of several micrometers within minutes of applying near-piconewton forces to the loci, which were found to be consistent with a Rouse polymer model. Overall, the results suggest the interphase chromatin is more fluid than gel-like. Through these experiments, the scientists were able to see that a range of forces exerted naturally in the nucleus, such as the forces applied by enzymes while replicating DNA, are sufficient to substantially alter the conformation of a chromosome. The study challenges conventional views about the physical nature of chromosomes, and allows for a better understanding of how these structures will behave under biological forces. This research was published in Science.
The magnetic nanoparticle method used by the researchers offers a potential tool for further study of the physics of chromosomes within the nuclei of living cells. Additionally, the information gained from the study could aid in the development of new physical models for chromosomes.