"Binding" or "Binding and Switching"? A Perspective on Resolving Conformational Changes of Surface-Attached...

Understanding the structural reconfiguration of a biomolecular receptor remains a topic of particular interest to the biosensing community. This is because conformationally changing receptors are commonly employed in biosensors to harness their capability to bind specifically to their target. Often, such receptors are attached to surfaces so that binding can be transduced into a measurable response. Doing so, however, can impose constraints on the possible configurations they can adopt. Such constraints can ultimately influence, for example, their receptor-target binding models or their affinity, which is essential to provide the desired analytical performances in biosensors. Motivated by the idea of gaining further insights into the impact of surface attachment on conformationally switching receptors attached to surfaces, we explore here the various surface-based techniques capable of monitoring structural changes. We decided to narrow our survey to techniques that have been applied to the investigation of nucleic acids to provide an overview of their key features. We envision that this will bring a broader perspective of the field and the challenges ahead with the hopes of "finding the switch" in surface-attached biomolecular receptors.