Molecular machines are fascinating devices that drive self-organization in cells. While the proteins involved in many mechanical processes like transport or cell division have been identified, the mechanical principles that govern their operation are poorly understood. For example, how much force can molecular machines generate; how are they regulated; and what limits their speed and efficiency? Currently, our research in cellular nanoscience focuses on developing and applying single-molecule fluorescence and force microscopy techniques - high-resolution optical tweezers and novel probes - to understand how molecular machines, such as kinesin motors, membrane proteins, and DNA repair proteins, work mechanically to fulfil their cellular function.
To perform single-molecule force and localization measurements, we develop and push the limits for high-resolution optical tweezers and complementary microscopy techniques with single-molecule sensitivity (TIRF, interference reflection, and light sheet microscopy).
We have developed an accurate, precise, and in-situ calibration technique for optical tweezers with back focal plane detection.
To broaden the scope and enhance resolution of single-molecule experiments, we develop custom-made nanoparticles and microspheres composed of coated high-refractive-index (titania and nanodiamonds), birefringent liquid crystalline, or semiconducting materials. These novel probes enable the generation of high forces, a high force, spatial or time resolution, the measurement of rotations, or the application of torques.
Mechanics of kinesin motors and microtubule-associated proteins
Kinesins walk on microtubules with a rotary hand-over-hand mechanism. To decipher their operation, we perform simultaneous translation, rotation, force and torque measurements on kinesins. In addition, we work on kinesins and microtubule-associated proteins involved in plant cytokinesis, microtubule alignment, dynamics, and length regulation.
The protein machinery responsible for DNA repair via homologous recombination forms nucleoprotein complexes. To resolve the repair mechanism, we work on measuring the complexation dynamics and energetics of single-strand annealing proteins.
To resolve how membrane proteins help to sculpture lipid bilayers, we work with giant unilamellar vesicles and curvature-sensitive membrane proteins.
Active particles provide new insight into fundamental questions of self-organization via collective phenomena and novel possibilities for applications like drug delivery. To understand how synthetic, self-propelled particles work, we measure forces and characterize the motion of active, enzyme driven colloids, or so-called micro- and nanomotors.
Erik Schäffer, Professor of Cellular Nanoscience