Nanoparticle biocoating to create ATP-powered swimmers capable of repairing proteins on the fly

Abstract

One of the most attractive futuristic challenges in nanomedicine is to create self-propelled nanorobots to scan and repair living tissues at the nano/microscale. Ideally, these devices should navigate using local, inexhaustible biomolecules as energy sources, while performing different functions, such as delivering drugs or repairing tissues. In this study, we combine nanotechnology and biotechnology to design a biocompatible propulsion system based on the molecular chaperone Hsp90, a heat-shock protein (Hsp) that, in the presence of adenosine 5′-triphosphate (ATP), undergoes nanoscale conformational changes while trapping and renaturing other proteins. We show how, subjected to ATP availability in the medium, Hsp90-functionalized particles significantly enhance their diffusion motion, being able to achieve ballistic motion, while keeping the ability to restore the activity of surrounding heat-inactivated proteins. This biomechanics-based propulsion mechanism represents a promising strategy for the design of self-propelled nanodevices capable of performing sophisticated tasks in live biological contexts that include sensing the environment, recognizing and capturing, folding, and restoring defective proteins on the fly. In the short term, Hsp90-driven nanodevices could be applied to improve industrial processes that require enzymatic catalysis and high temperatures. But in the medium to long term, this bioactive coating could be used in the design of nanomachines that, like mini-robots, navigate the complex body cavities of biological tissues, deliver therapies and/or remove misfolded proteins in disorders such as Alzheimer's or Parkinson's disease.