ABSTRACT
Molecular-level control over surface chemistry and topology is critical for the design of biologically active synthetic surfaces. Such surfaces must present active biological ligands in defined confor-mations, orientations, concentrations, and spatial distributions so as to foster biospecific interactions and inhibit nonspecific ones. Self-assembled monolayers (SAMs)—spontaneously organized monomolecular assemblies at solid surfaces-provide an elegant and versatile means to endow synthetic surfaces with such exqui-site level of control at the molecular level. This chapter reviews the essential physical-chemical foundation for the preparation, struc-ture, and formation mechanisms of SAMs; presents their amenabil-ity for spatial control using tools of micro-and nanopatterning; and
highlights their enabling capacity for a broad range of biomolecular functionalization. 1.1 IntroductionThe two main limiting applications for attachment of biomolecules and bioentities (here broadly defined as complex biological structures hierarchically constructed from simpler biomolecular units) onto synthetic surfaces are biomedical implants [1, 2] and analyses or characterization of biological activity and function [3]. The second case involves a range of applications, which include biological assays or biosensing and scientific applications involving detailed biophysical and/or biochemical analyses for establishing structure-function correlations. In these (and many other) applications, it is critical that the synthetic surface provide a local region of contact, which is compatible with specific aspects of the natural biological function of contacting bioentities. In the first case of implants above, the requirements are obvious; they are to avoid or minimize adverse reactions with the local physiological environment and promote integration with the host by fostering desired biological interactions. In the case of analytical and fundamental biophysical or biochemical characterization, the degree of biological function required to be recapitulated at the synthetic material surface depends completely on the chosen task at hand. In addition, for these applications, it is necessary that the surfaces provide the capability to sense, modulate, or transduce the presence and perhaps even the specific biological activity of the bioentities. Thus, to be general, one must take the view that the design of such biologically active synthetic surfaces requires exquisite molecular-level control over their surface chemistry and topology [4]. It is becoming increasingly well appreciated that biospecific interactions responsible for a biological function, which a synthetic surface must reproduce, are almost invariably sensitive to subtle variations in conformation, orientation, concentration, and spatial distribution of biomolecules. Thus, the native inter-and intramolecular physical properties of these biomolecules in their surface-bound state must be recapitulated onto the synthetic surface. Moreover, many biological entities (e.g., proteins, antibodies, lipids,
cells, viruses, and bacteria) exhibit tendencies for “promiscuous” binding to synthetic material surfaces via nonspecific physical-chemical interactions producing undesirable “noise,” which must be mimimized [5]. For instance, biosensors used in biomedical diagnostics, must present specific receptor molecules onto transducer surfaces in their native conformations [6]. This attachment must be stable over the course of a binding assay; should present sufficient binding sites to the solution, namely, aqueous, phase to interact with the analyte; and must resist nonspecific binding [7]. Similarly, synthetic implants must resist fouling or nonspecific adsorption of interacting biological entities, integrate with the host tissue, and exhibit long-term stability in their surface compositions [8]. SAMs, toward this end, provide a versatile strategy to prepare biofunctional surfaces [4] with molecularly tailored physical-chemical properties [9, 10]. These organized monomolecular assemblies are formed simply by the spontaneous adsorption of molecular constituents from the solution (or vapor) phase onto specific native or synthetic surfaces [11, 12]. Candidate molecules consist of a functional attachment “headgroup” separating the independently selected end group by a discrete-length tail, typically, consisting of an aliphatic chain-for example, X-(CH2)n-Y. To be even more general, an aromatic ring structure or other spacer unit, which itself is nonpolar and can bear both attachment and tail groups, can be used, although these approaches are not commonly employed for biological applications. The surface binding headgroup has a specific affinity for the arrays of single or multiple, distinct adsorption sites at the material surface. This molecule-surface recognition landscape (Y-S), together with the intermolecular tail-tail interactions between the adsorbate molecules-for example, (CH2)n | (CH2)n-and the interfacial interactions of the exposed end groups with the surrounding ambient phase (e.g., X-solvent interface) provides the necessary driving forces for the production of well-defined molecular assemblies [13]. A simple schematic illustrating synthetic surfaces with SAMs for biological applications is shown in Fig. 1.1. The figure shows a local region with biomolecular species adhering to the SAM surface immersed in a medium, which is generally aqueous, ranging from purely laboratory controlled phases to more complex in vitro or in vivo aqueous environments.
