Chemically well-defined self-assembled monolayers for cell culture: toward mimicking the natural ECM

The extracellular matrix (ECM) is a network of biological macromolecules that surrounds cells within tissues. In addition to serving as a physical support, the ECM actively influences cell behavior by providing sites for cell adhesion, establishing soluble factor gradients, and forming interfaces between different cell types within a tissue. Thus, elucidating the influence of ECM-derived biomolecules on cell behavior is an important aspect of cell biology. Self-assembled monolayers (SAMs) have emerged as promising tools to mimic the ECM as they provide chemically well-defined substrates that can be precisely tailored for specific cell culture applications, and their application in this regard is the focus of this review. In particular, this review will describe various approaches to prepare SAM-based culture substrates via non-specific adsorption, covalent immobilization, or non-covalent sequestering of ECM-derived biomolecules. Additionally, this review will highlight SAMs that present ECM-derived biomolecules to cells to probe the role of these molecules in cell-ECM interactions, including cell attachment, spreading and 'outside-in' signaling via focal adhesion complex formation. Finally, this review will introduce SAMs that can present or sequester soluble signaling molecules, such as growth factors, to study the influence of localized soluble factor activity on cell behavior. Together, these examples demonstrate that the chemical specificity and variability afforded by SAMs can provide robust, well-defined substrates for cell culture that can simplify experimental design and analysis by eliminating many of the confounding factors associated with traditional culture substrates.