Protein Rigid Organization for Powered Engineered Locomotion

Objective

Proteins are nature's nano-machines, driving essential biological processes, including those involving mechanical work: DNA replication, membrane remodelling, and cargo transport. Synthetic protein motors have enormous potential in health and material applications and could help us unravel the mechanism of natural protein motors. At present, the ability to design protein motors from scratch remains beyond our reach. The PROPEL project aims to address this challenge by constructing the first genetically encodable de novo protein walkers capable of powered, directional motion along designed protein tracks. We will combine cutting-edge AI design tools with sophisticated single-molecule tracking experiments to create protein motors based on a driven Brownian ratchet mechanism. This approach represents a significant leap forward in synthetic molecular machines, surpassing the current state-of-the-art in DNA nanotechnology by leveraging the chemical versatility, genetic encodability and hyper-stability of designed proteins. Key objectives of PROPEL include designing rigid asymmetric tracks (Objective 1), creating specific anchors to control where and when tracks grow (Objective 2), integrating power sources such as alternating electric fields, enzymatic reactions, and enhanced diffusion effects (Objective 3), and demonstrating cargo transport applications such as force generation and active motion in live cells (Objective 4). PROPEL's innovation lies in its ability to create entirely de novo protein motors and tracks that expand our understanding of molecular processes and open new avenues for bionanotechnology. Potential applications range from synthetic cell machinery and precision medicine to smart materials and programmable nanorobots. By creating the first powered and directed de novo protein walker, PROPEL will advance our understanding of molecular transport processes and lay the groundwork for future protein-based nanorobots.