Inflammation is a protective response of the immune system to infection or physical damage that is mediated in part through the recognition of molecular patterns associated with microbes or released by necrotic cells following tissue injury. In a study published in Cell Chemical Biology (see also Cell Chemical Biology Previews), the teams of David Alsteens and Bernard Knoops have used force-distance curve-based atomic force microscopy (AFM) to investigate the molecular mechanisms by which extracellular human peroxiredoxin-5 can activate a proinflammatory response. Peroxiredoxins are known for their intracellular roles as cytoprotective antioxidant enzymes, protein chaperones, modulators of peroxide signaling and redox relays but recently their function as extracellular alarmin to trigger an inflammatory response has been proposed. The LIBST teams used this novel approach in immunology to demonstrate and measure specific binding of human peroxiredoxin-5 to Toll-like receptor 4 on purified receptors and live cells. Moreover, they observed that cells probed with a single peroxiredoxin-5 molecule became stiffer, which is particularly relevant in the context of inflammation. Indeed, artery stiffening or reduced arterial compliance is a prominent feature of systemic hypertension, pulmonary hypertension, and other vascular-related diseases with a strong chronic inflammatory component.