Micro- and nanostructured devices for cell studies

Cell culture is a fundamental and valuable tool for modern biomedical research. The purpose of this work has been to expand the possibilities and methods of cell culture through engineering of the cell culture substrate. A range of micro- and nanofabrication tools were used to structure new material systems and combinations that could be applied as cell interfaces. Several different material systems and applications were explored. Soft lithography was used to produce patterns of cell-adherent polydopamine on cell-repellent poly(vinyl alcohol) hydrogels as an effective and stable cell patterning and patterned co-culture platform. Microscopic wells and a reference grid were thermomoulded into aclar polymer films and used as substrate enabling efficient correlative 3D optical and electron imaging of the same cells. Surfaces with high aspect ratio CuO nanowires were controllably produced and explored as a surfacebased delivery platform for genetic material to cultured cells. Particular emphasis was put on better understanding the cell-nanowire interface, with the important result that membrane engulfment of the nanowires likely inhibits efficient gene transfer. The idea of better understanding the interface between cells and surface nanostructures was further pursued in the development of a tunable, high aspect ratio polymer nanostructure platform. This platform enabled high resolution optical imaging of cell interactions with the polymer nanostructures. Details of cell morphology, membrane conformations and cytoskeletal organization in response to nanopillars and nanolines was explored. Further, this platform was applied to study the dynamics of migrating cells on polymer nanopillar arrays, showing strong interactions that alter migration mechanisms and speed. In summary, this work demonstrates how the bio-focused design of micro- and nanostructured platforms can pave the way to novel, functional devices and surfaces. In turn such devices contribute to furthering the use of advanced cell culture systems for modern biomedical research