College 9 Seminar | Wound Healing – Redefining Fibrinogen Adsorption at the Air–Water Interface: an Intriguing Story with Multiple Layers
21/10/2026 - 14h00 to 16h00Layer-by-layer self-assembled structures of the blood-clotting glycoprotein fibrinogen have been resolved at a fluid interface using neutron reflectometry and complementary techniques to reveal an unexpected mechanism that contradicts a long-established adsorption model. The widely accepted monolayer tilt model, inferred over two decades ago from ellipsometry data, involves progressive tilting of a monolayer of fibrinogen molecules from parallel with the interface with increasing interfacial coverage until, at saturation, the molecules adopt a more vertical conformation.
Our new structural framework is fundamentally different in that fibrinogen is shown unequivocally to orient parallel with the interface in multiple discrete layers, and, with increasing bulk concentration, there is enhanced layer thickness, greater coverage of the submerged layers and, in cases, the presence of additional layers. The varying layer thickness is attributed to changes in the conformational freedom of different monomer/dimer interactions at the interface. The driving forces for the layer-by-layer self-assembly are rationalized in terms of intermolecular electrostatic interactions, hydrogen bonding and hydration, and conformational adaptability.
The universal relevance of our new model is demonstrated by data from experiments performed in acidic and basic buffers over orders of magnitude in bulk concentration and ionic strength. The experiments were performed using neutron reflectometry (NR) on the FIGARO instrument at the ILL between 2012 and 2024 through international collaboration involving researchers from Spain, Chile, France and the UK. The measurements enabled resolution of the protein surface structures in finer detail than had been previously resolved, following on from recent focus in projects on drug interactions with lipid membranes that will feature in the introduction of the presentation.
Our new findings on protein structures have broad implications for interfacial protein behavior, as they help to explain the mechanism of sealing open wounds through scab formation at the protein-rich fluid interface of blood. Links to the enhanced competition for interfacial area from plasma proteins over phospholipids impairing lung function in patients with acute respiratory distress syndrome have already started to be explored using NR. The significance of links to protein biofouling of implants and biosensors used for glucose monitoring of diabetes patients, which will start to be explored using the D17 reflectometer the day after this seminar, will be discussed during the presentation.