Forces are fundamental to the function of living systems, driving natural processes such as tissue morphogenesis and locomotion, as well as our ability to interact with living matter, for instance, in the context of therapeutic interventions. Magnetic fields, in particular, offer distinct advantages in biomedical applications due to their ability to penetrate tissues non-invasively and exert forces remotely. Beyond delivering mechanical stimuli, magnetic fields can facilitate the transport of objects through biological media. This work spans several approaches to generate forces using magnetism at the nano- and microscale, including magnetic field gradients, rotating magnetic fields, and homogeneous magnetic fields. These strategies are applied in various biomedical contexts to enable characterization, manipulation, and transport of nano- and microscale objects. Furthermore, when direct mechanical forces alone are insufficient to achieve the desired outcomes, the thesis investigates an alternative strategy to locally disrupt a principal biological barrier, thereby facilitating transport within complex biological environments. The thesis begins with a quantitative analysis of the force ranges achievable through different magnetic strategies and their implications for biomedical applications. Subsequently, a method is developed to quantify the magnetic properties of individual particles suspended in liquid using magnetic field gradients. Magnetic stimuli are then applied to cells with the aim of developing tools to investigate mechanotransduction. In this context, cell monolayers are mechanically stimulated using embedded ferrofluid droplets, which serve as magnetically responsive actuators under homogeneous magnetic fields. This platform is subsequently enhanced by introducing a magnetizable probe that locally perturbs the uniform magnetic field, thereby generating spatially confined magnetic field gradients at the microscale. A similar microscale gradient strategy is employed in a separate experimental setup to guide the sprouting of cells that have internalized magnetic nanoparticles, offering a tool for applications in tissue engineering. The final section of the thesis explores the transport of nano- and microscale objects for ophthalmological applications, with the aim of enabling targeted delivery of drugs or therapeutic genes within the eye. The work first addresses transport through potential vitreous substitutes, which are relevant in the treatment of eye conditions. Using magnetic field gradients, suitable hyaluronic acid–based formulations are identified that permit the penetration of nano- and microparticles. Building on these findings, the thesis demonstrates the active propulsion of helical nano- and micropropellers within these materials using rotating magnetic fields, thereby establishing the feasibility of magnetically guided delivery systems in hydrogels that are designed to replace the vitreous body. Finally, the thesis investigates targeted nanoscale transport to retinal cells, where the successful delivery of therapeutic genes holds promise for treating a range of retinal disorders that can lead to blindness. Initial experiments using ex vivo porcine models are used to asses the property of natural barriers impeding nanoscale transport. To address limited permeability, a more refined strategy is introduced, in which enzymes are attached to microparticles to enable localized degradation of the primary biological barrier, thereby facilitating access to the retina. This approach results in enhanced nanoparticle transport across the barrier. Collectively, this work establishes methods for magnetic-field based force application, targeted manipulation, and controlled transport at the nano- and microscale within complex biological environments. This work introduces novel tools and strategies that advance both mechanobiology and targeted ocular delivery systems.
Lucie Motyčková (Thu,) studied this question.