Single molecule mechanics of myosin motors using optical tweezers at sub-millisecond time resolution

• Applicant: Professorin Dr. Claudia Veigel
• Subject Area: Biophysics
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 385892061

My research focuses on the acto-myosin cytoskeletal system on which a myriad of motile cellular functions is based, ranging from muscle contraction to endo-and exocytosis, cell locomotion, cytokinesis and even signal transduction in hearing. In order to understand the structural dynamics and functional properties of the large variety of myosin motors that are organised into highly specialised transport or force sensing systems in the cell, we need to push the limits of the temporal and spatial resolution of single-molecule technology to the nanometre and microsecond range. This will make it possible to finally connect the single molecule mechanical studies to molecular dynamics simulations and to obtain a truly atomic understanding of the molecular dynamics of these cellular nano-machines. We are using single-molecule fluorescence and mechanical techniques based on custom-built optical tweezers that enable us to study the pico-Newton forces and nano-metre displacements produced by single motor proteins. Our aim is now to develop an optical tweezers apparatus with a time resolution in the sub-millisecond range. With the improved time resolution we hope to resolve the early events of the acto-myosin interaction, including the transition from weak non-specific to stereospecific strong binding states. These parts of the chemo-mechanical cycle have remained illusive to date. In this project we will focus specifically on two classes of myosin with intriguing cell biological functions; (i) an ancient myosin class XXI, the only myosin expressed in the human pathogenic Leishmania parasite which has a vital role for the parasite survival, and (ii) human myosin class IX, which plays a critical role in reorganisations of the lamellipodium in migrating cells and during cell polarisation in morphogenesis. The mechanical properties of these two medically and in terms of basic research important classes of myosin are unclear and they have not been studied at the single molecule level before.

• DFG Programme: Research Grants