Arqué, Xavier "Unraveling the Fundamental Aspects of Enzyme-powered Microrobots." PhD
, University of Barcelona, 2023
Keywords/Fields of Study : Microrobot, Nanorobot, Self-propulsion, Active Navigation, Microscopy Visuals, Active Motion, Enzyme, Biocatalysis, Active Matter, Micromotor, Nanomotor, Biochemistry, Silica, Urease, Catalase, Microswimmer, Nanoswimmer
Link to Full Thesis, 188
pages, written in English
, copyright Thesis licensed under the Creative Commons Attribution-ShareAlike 4.0 Spain License (CC BY-SA 4.0 ES)
Abstract: Enzyme-powered robots are micro- and nanosized particles that self-propel thanks enzymes attached on their surface that asymmetrically catalyze the chemical conversion of substrate to product molecules. Recently, these tiny devices have been applied for a plethora of applications ranging from biomedicine to decontamination, sensing, and bacteria elimination. However, the fundamental aspects of enzyme-powered navigation are not well understood, and with the emerging properties of collective behavior, bot-to-bot communication, and response to external stimuli these nanosystems pose an appealing instrument for microvisual artistic practices. This thesis appears as a response to the need of unraveling these fundamental aspects of biocatalytic propulsion.
The initial object of study is the effect of the intrinsic properties of enzymes on active motion. Different enzymes are tested to power motion of silica microspheres while expand the library of available engines. Their bubble-free and directional active motion is analyzed under different concentrations of substrates and inhibitors. In parallel, we test the enzymatic activity and structural flexibility through molecular dynamics simulations. Form this we conclude that active motion is directly dependent on the catalytic rate, and that conformational changes should always be considered since they constitute a prerequisite for catalysis.
Further, the extrinsic conditions are studied in terms of the surrounding media composition. Through wet lab experiments and a physical model, we analyze the negative influence of external ionic species on the active motion mechanism of urease enzyme silica-based microbots. We discard any effect of sedimentation and surface interaction through 3D tracking using digital holographic microscopy. Hence, the influence of external ions on navigation sheds some light on the ionic self-diffusiophoretic mechanism behind the propulsion of enzymatic bots. This effect is circumvented by coating the bot surface with a charged polymer, which allows for motion under intermediate ionic strengths.
Finally, the aforementioned knowledge is used for the implementation of enzymatic silica bots for the in vivo treatment of bacterial infections. Antimicrobial peptides are coated on the bots and the system is thoroughly characterized. The urease micro- and nanobots are tested against different planktonic bacteria to check their effectivity and antimicrobial mechanism. After, the bots are applied at an extreme of an infected wound on the skin of a murine model. Disinfection is only achieved using actively moving bots with antimicrobial peptide, and the alternative passive treatments only treat the infection locally.
Additionally, a novel type of microbot is fabricated with a metal-organic framework structure that contains a multisized porosity. This is exploited to encapsulate the catalase enzyme inside the mesoporoes and power navigation by consuming hydrogen peroxide and releasing a thrust of oxygen bubbles. The free micropores in the structure are used to encapsulate a model contaminant while navigating as a proo-of-concept for environmental applications.
This thesis constitutes a relevant step forward on elucidating the intrinsic and extrinsic fundamental aspects that are key for enzyme-powered micro- and nanobots and uses the knowledge acquired to improve future implementations. Further, these biohybrid nanosystems are the initial examples of artistic endeavors in active matter as bottom-up synthetic livings with complex and aesthetically engaging motion dynamics.
Department: Smart Nano-Bio-Devices Lab (Prof. Samuel Sánchez) in the Institute for Bioengineering of Catalonia (IBEC)
, University of Barcelona
Advisor(s): Samuel Sánchez
