Seeing (and feeling) is believing. Assessing biomolecular interactions across scales using fluorescence optical tweezers

Biological processes involving proteins interacting with nucleic acids, cell membranes or cytoskeletal filaments are key to cell metabolism and hence to life in general. Detailed insights into these processes provide essential information for understanding the molecular basis of physiology and the pathological conditions that develop when such processes go awry. The next scientific breakthrough consists in the direct, real-time observations and measurements of the most fundamental mechanisms involved in biology Single-molecule technologies offer a powerful opportunity to meet these challenges and to study dynamic protein function and activity in real-time and at the single-molecule level.

Here, we present our efforts for further enabling discoveries in the field of biology and biophysics using the combination of optical tweezers with correlative fluorescence microscopy (widefield, TIRF, confocal and STED) and label-free Interference Reflection Microscopy (IRM). We present several examples in which our technology has enhanced the understanding of basic biological phenomena, ranging from protein structure to genome editing, chromatin organization, DNA damage repair, phase separation and cytoskeletal structure formation. 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.