Probing ligand-receptor bonds in physiologically relevant conditions using AFM

Lo Giudice, Cristina [UCL] Dumitru, Andra-Cristina [UCL] Alsteens, David [UCL]

Cell surface receptors, often called transmembrane receptors, are key cellular components as they control and mediate cell communication and signalling, converting extracellular signals into intracellular signals. Elucidating the molecular details of ligand binding (cytokine, growth factors, hormones, pathogens,...) to cell surface receptors and how this binding triggers conformational changes that initiate intracellular signalling is needed to improve our understanding of cellular processes and for rational drug design. Unfortunately, the molecular complexity and high hydrophobicity of membrane proteins significantly hamper their structural and functional characterization in conditions mimicking their native environment. With its piconewton force sensitivity and (sub)nanometer spatial resolution, together with the capability of operating in liquid environment and at physiological temperature, atomic force microscopy (AFM) has proven to be one of the most powerful tools to image and quantify receptor-ligand bonds in situ under physiologically relevant conditions. In this article, a brief overview of the rapid evolution of AFM towards quantitative biological mapping will be given, followed by selected examples highlighting the main advances that AFM-based ligand-receptor studies have brought to the fields of cell biology, immunology, microbiology, and virology, along with future prospects and challenges.