Surface engineering and soft lithography in biology

The interactions of complex biological media, typically solutions of proteins and suspensions of cells, with surfaces are not well-understood. The need to control these interactions for applications in biomedicine and biotechnology raises challenging questions on the biophysical parameters that govern the interactions. An understanding of the relationship between the structure of a surface and its response to biological media requires the ability to engineer the properties of surfaces and to study that response. Part I describes the use of self-assembled monolayers (SAMs) as model surfaces for the study of the adsorption of proteins and the adhesion of cells (Appendix I). The ability to control the properties of the surfaces of microstructures fabricated by soft lithography is a key component of methods to pattern the attachment of mammalian cells to surfaces (Part (II). Chapter one introduces the techniques of soft lithography and surface engineering, and it illustrates their application to problems in biology and biochemistry. In Part I, the model organic surfaces of SAMs were used to develop methods for studying: (i) the adsorption of proteins to hydrophobic surfaces, and (ii) the resistance of surfaces to the adsorption of proteins (Chapters 3–5). Mixed SAMs with well-defined distributions of hydrophobic groups made it possible to study the hydrophobic adsorption of proteins (Chapter 2). The results, interpreted with a simple hard-sphere model, are consistent with the hypothesis that proteins spread upon adsorption to surfaces; parameters for minimizing the spreading of proteins on surfaces are provided. SAMs were the basis for the development of a convenient screening method for elucidating structure-property relationships of surfaces that resist the adsorption of proteins (Chapter 3 and Appendices II–IV). The ability of a SAM to resist the adsorption of proteins, however, did not correlate with its ability to resist the adhesion of bacterial and mammalian cells (Chapter 4). The design principles of SAMs that resist the adsorption of proteins (Chapter 3) were applied successfully to the synthesis of thin polymeric films that resist the adsorption of proteins and the adhesion of bacteria (Chapter 5).; Microstructures fabricated using soft lithography were used as substrates or masks for the development of methods to pattern cells in part II. The combination of SAMs with polymeric microstructures was useful to create and study patterns of cells (Appendices V and VI). The behavior of liquids on contoured microfabricated substrates made it possible to pattern the surfaces of those substrates with proteins; this method was illustrated with the selective deposition of adhesive matrix proteins and mammalian cells in microwells. The study of cell migration from a pattern—something that is difficult to do with SAMs—is made possible by microstructures (Chapter 7). Thin polymeric films with through-holes that are in contact with a substrate, and surfaces tailored to prevent cell adhesion, were used as masks to direct the adhesion of mammalian cells to the substrate—through the holes. Removal of the thin films made it possible for the cells to spread from the initial pattern onto the previously-masked surface. The use of microfluidic systems to pattern the delivery of small molecules to the intracellular milieu—a unique capability of systems fabricated with soft lithography—is illustrated in appendices VIII–IX.