Mediating Cellular Orientation And Migration By The Internalized Magnetic Particles Under Field Direction

With the rapid development of nanobiotechnology, the interfacial interactions between nanomaterials and biological systems including cells and biomembranes have attacted increasing interest. Among various nanomaterials, magnetic nanoparticles(MNPs) have been widely investigated for the applications for biomedical purpose due to the good biocompatibility of them. Besides being regarded as a promising contrast enhancing agent for the in vivo magnetic resonance imaging(MRI), in recent years, significant development has been made in the straightforward applications of bio-functionalized MNPs for manipulating cells(including proteins) both in vitro and in vivo, including cell capture and/or separating, in vivo cell targeting and tracking, multicellular construction for tissue engineering, modulation of cellular behavior such as migration and focal adhesion, etc. One of the most important advantages of MNP-based cellular manipulation is the quick response of MNPs to an external magnetic field which offers a unique way to modulate cellular behavior in a remote and non-contact mode, which is especially attractive for the in vivo applications.In this thesis, we realized for the first time the modulation of cellular behaviors including orientation and migration based on internalized Fe3O4 nanoparticles. This work mainly consists of three parts:(1) the endocytosis of Fe3O4 nanoparticles. We monitored the dynamic biological process of cellular endocytosis of Fe3O4 particles with different particle concentrations. We further confirmed the intracellular localization and the cytotoxicity of the MNPs.(2) modulation of cellular behaviors based on the internalized Fe3O4 particles, which worked in a particle-concentration dependent manner. At low MNP concentrations, the internalized particles separately distributed surrounding the nuclei, and somewhat influenced the orientation of cells along the direction of the external magnetic field. In contrast, when the concentration of MNP was high enough, the particles formed clusters within cells and moved towards the edges in magnet direction, leading to an obvious morphological change and subsequently a directed migration of cells.(3) based on combination of the internalized Fe3O4 particles and the external magnetic field, we realized the modulation of multicellular behaviors. In addition, we investigated the interactions between another type of bionanomaterials, graphene oxide, and biomembrane, to learn about the interaction mechanism between them.Based on MNP, this work shows a novel way to manipulate cell behaviors with excellent biocompatibility. The results not only shows importance for biological researches, but also promises potential applications in biomedical purposes such as targeted delivery and tissue engineering.