Single-molecule methods are promising to provide deep insight into all biological problems. Methods include among others single-molecule fluorescence and force measurement techniques. Such measurements are limited by Brownian motion that puts bounds to the spatiotemporal resolution and by nonspecific interactions of the molecules of interest to probes and surfaces that are involved in the measurement. Several novel methods were developed to reduce nonspecific interactions and improve the spatiotemporal resolution of single-molecule assays. Firstly, a highly reproducible supported solid lipid bilayer platform was developed which provides specific and load bearing attachments with less nonspecific interactions of biomolecules and probes to the surface. Thus, the lipid bilayer platform enabled fluorescence and force measurements to study the mechanics of single DNA molecules and molecular motors. One such molecular motor is kinesin that transports vesicles along microtubules. How the motors step, detach, and cooperate with each other is still unclear. An ideal tool, to study the mechanics of kinesin are optical tweezers. Optical tweezers use microspheres as handles for measuring piconewton forces generated by kinesin. However, micron-sized probes with a low refractive index limit the spatiotemporal resolution. To overcome this limit, high refractive index germanium nanospheres were synthesized. Instead of 8-nm steps, kinesin-1 motors were found to take 4-nm center-of-mass steps with alternating step durations depending on force and ATP. By these measurements, a long-standing controversy was resolved bringing together the kinesin stepping and detachment behavior. In the long-term, employment of this novel probes that enable an ultrahigh resolution opens up new avenues for detailed investigations and new discoveries of conformational changes that are key for the biological function of many other molecular machines.

Other parts of my research focus on development of different types of nanomaterials with their therapeutic and drug delivery application in treating Alzheimer’s and Cancer. Porous silica materials are often used for drug delivery. However, systems for simultaneous delivery of multiple drugs are scarce. In our studies we have developed and shown that anisotropic and amphiphilic dumbbell core–shell silica microparticles with chemically selective environments can entrap and release two drugs simultaneously. In the long term, amphiphilic nano and micro particles may open up new strategies for drug delivery.