Biological processes performed by proteins interacting with DNA/RNA, cell membranes or other proteins are key to cell metabolism and life. In fact, detailed insights into these processes provide essential information for understanding the molecular basis of life and the pathological conditions that develop when such processes go awry.
Being able to manipulate, measure and observe - direct and in real-time - on the single molecule level are crucial in order to validate and complete the current biological models. Some current techniques are exceptionally equipped to study structure and composition of single molecules (e.g. X-ray Crystallography or CryoEM). On the other hand, dynamic functionality of molecular mechanisms can be studied with beautiful techniques such as live cell microscopy or SPR, which requires many molecules to pass the detection threshold.
Single molecule technologies combines these two crucial aspects : single molecule scale and dynamics. The next scientific breakthroughs consists of the direct, real-time observations, manipulations and measurements of the individual mechanisms involved in biological processes. By actively introducing, manipulating and measuring single molecules and their interactions, complex molecular mechanics can be addressed in great detail.
Here, we present our efforts for further enabling discoveries in the field of biology and biophysics using the combination of optical tweezers with correlative confocal fluorescence microscopy. We present several examples in which our correlative technologies enhanced the understanding of DNA binding proteins, protein folding and dynamics, protein-membrane interaction and genome structure and organization.
​ Furthermore, we show that advances in hybrid single-molecule methods can be turned into an easy to-use and stable instrument that has the ability to open up new avenues in many research areas.

​