Bioactive Patterns at the 100-nm Scale Produced Using Multifunctional Physisorbed Monolayers

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Bioactive Patterns at the 100-nm Scale Produced Using Multifunctional Physisorbed Monolayers Janos Vörös, Thomas Blättler, and Marcus Textor Abstract Recently, a variety of patterning techniques have reached feature sizes of 100 nm or less, a size range very relevant to biology. Proteins, vesicles, and macromolecular assemblies can now be handled and specifically placed onto predefined artificial patterns, triggering defined functions in cells and revealing the details of cell–surface interactions. Simultaneously, novel surface chemistries have been developed that are able to induce specific bioresponses (e.g., mimicking the features of the extracellular matrix) and at the same time suppress the nonspecific effects of complex biological solutions. This article reviews the basic principles and properties of multifunctional physisorbed monolayers that can be used in combination with nanopatterning techniques to create biologically relevant surface features. Furthermore, selected examples of nanopatterns created by novel combinations of different top-down and bottom-up approaches are presented, including systems with specific bioligands, proteins, vesicles, and cells. Keywords: cells on nanostructures, multifunctional monolayers, nanobiotechnology, nanopatterning, protein patterning.

Introduction Techniques to produce chemical patterns and topographical structures on surfaces at the micron scale have been developed and successfully applied for many years in a variety of fields ranging from microelectronics, microelectromechanical systems (MEMS), micro-optics, biosensors, and tissue engineering to fundamental studies in cell biology. BioMEMS, for example, are micrometer-sized devices designed for specific biological applications, including experiments performed on the scale of a

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single cell.1 More recently, the rapid development of nanotechnology tools has opened up new approaches to producing welldefined patterns and structures with dimensions of 100 nm or less.2 The interest in surfaces with nanometer features is at least as widespread as interest in the micrometer-sized devices. In biosensing, medical diagnostics, and lab-on-a-chip applications, improved detection sensitivity, shortened reaction time, reduced sample volume, parallel detection of a large number

of analytes, and the development and use of novel transduction techniques (e.g., based on nanostructures and nanoparticles) have driven the exploitation of nanobiotechnology in these emerging fields.3–6 Moreover, nanosystems, defined as having features or characteristic lengths between 1 nm and 100 nm, exhibit special and interesting physical characteristics such as quantized excitation, single-electron tunneling, and metal–insulator transition.7 Living cells react to nanopatterns and nanostructures down to the low-nanometer range, with surface topography and local surface chemical composition being cues that are sensed by cells.8–10 Studies of cells attached to adhesive patterns the size of individual cells (typically tens of micrometers) have highlig