In our lab, we have developed the combination of optical tweezers and single-molecule fluorescence microscopy as a powerful tool to study biomolecules and biomolecular complexes. Combining these two technologies allows holding a sample molecule or complex, extending or deforming it, and measuring forces acting on it, while, at the same time, visualizing it with single-molecule sensitivity. We have applied this approach to different biological systems, including DNA, whole chromosomes, cytoskeletal components and membranes. Here, I will explain the concept of the technology, its potential and limitations. I will explain the technology by highlighting its application to our research on the mechanical properties of DNA and force-induced conformational transitions. I will also discuss our latest breakthroughs in applying this technology to intact mitotic human chromosomes, which provide novel insights in the mechanical properties of chromosomes and the way they are condensed in mitosis.
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