Fundamental Aspects of Enzyme-Powered Micro- and Nanoswimmers.

Self-propulsion at the nanoscale constitutes a challenge due to the need for overcoming viscous forces and Brownian motion. Inspired by nature, artificial micro- and nanomachines powered by catalytic reactions have been developed. Due to the toxicity of the most commonly used fuels, enzyme catalysis has emerged as a versatile and biocompatible alternative to generate self-propulsion. Different swimmer sizes, ranging from the nanoscale to the microscale, and geometries, including tubular and spherical shapes, have been explored. However, there is still a lack of understanding of the mechanisms underlying enzyme-mediated propulsion. Size, shape, enzyme quantity and distribution, as well as the intrinsic enzymatic properties, may play crucial roles in motion dynamics. In this Account, we present the efforts carried out by our group and others by the community on the use of enzymes to power micro- and nanoswimmers. We examine the different structures, materials, and enzymes reported so far to fabricate biocatalytic micro- and nanoswimmers with special emphasis on their effect in motion dynamics. We discuss the development of tubular micro- and nanojets, focusing on the different fabrication methods and the effect of length and enzyme localization on their motion behavior. In the case of spherical swimmers, we highlight the role of asymmetry in enzyme coverage and how it can affect their motion dynamics. Different approaches have been described to generate asymmetric distribution of enzymes, namely, Janus particles, polymeric vesicles, and non-Janus particles with patch-like enzyme distribution that we recently reported. We also examine the correlation between enzyme kinetics and active motion. Enzyme activity, and consequently speed, can be modulated by modifying substrate concentration or adding specific inhibitors. Finally, we review the theory of active Brownian motion and how the size of the particles can influence the analysis of the results. Fundamentally, nanoscaled swimmers are more affected by Brownian fluctuations than microsized swimmers, and therefore, their motion is presented as an enhanced diffusion with respect to the passive case. Microswimmers, however, can overcome these fluctuations and show propulsive or ballistic trajectories. We provide some considerations on how to analyze the motion of these swimmers from an experimental point of view. Despite the rapid progress in enzyme-based micro- and nanoswimmers, deeper understanding of the mechanisms of motion is needed, and further efforts should be aimed to study their lifetime, long-term stability, and ability to navigate in complex media.