In our lab, we have developed different combinations of optical tweezers and single-molecule fluorescence microscopy as powerful tools to study DNA and chromosomes. Combining these two technologies allows holding a DNA molecule or chromosome, extending or deforming it, and measuring forces acting on it, while, at the same time, visualizing it with single-molecule sensitivity. This equipment is now available to researchers worldwide from our spin-off company LUMICKS B.V. In my presentation I will explain the concept of the technology, its potential and limitations. I will focus on our research on the mechanical properties of DNA and force-induced conformational transitions. In our latest studies we have focused on the mechanical stability of condensed, mitotic chromosomes isolated from human cells. We have found that these chromosomes stiffen unusually under force. We show now, using fluorescence microscopy that this nonlinear mechanical response is caused by intrinsic mechanical heterogeneity within the chromosomes.
Erwin J.G. Peterman (Sun,) studied this question.