Bringing understanding of how fibrinogen behaves

By webmaster [at] nano [dot] lu [dot] se (Evelina Lindén) - published 4 September 2026

Two people in a laboratory. — During the pandemic, he spent time analysing structural data of how fibrinogen gathered at liquid surfaces. “Then after returning to work at the University, I applied additional experimental methods”, says post doc Glenn Coope. Photo: Johan Persson

How blood-clotting proteins arrange themselves at fluid interfaces may be more complex than previously thought. New research presented by Glenn Coope et al., using neutron reflectometry and complementary techniques, shows that fibrinogen does not simply tilt into a single layer, as previously believed, but instead forms multiple, distinct layers – a discovery with implications for wound healing, lung disease, and immune responses to nanoparticles.

In a new study, “Redefining Fibrinogen Self-Assembly at the Air–Water Interface: An Intriguing Story with Multiple Layers”, Glenn Coope and his fellow authors redefine how the key blood‑clotting protein fibrinogen behaves when it contacts air, overturning two decades of scientific consensus on wound healing.

The discovery could have far-reaching implications for the treatment of clotting disorders like haemophilia or the healthcare for patients on blood thinners like warfarin, as scabs forming on the surface of blood are vital to sealing a wound and keeping the site free of infection. It could also explain aspects of how a lung can collapse in acute respiratory distress syndrome (ARDS), as fibrinogen disrupts the oily layer that keeps the airways open during breathing.

It may also transform the design of biosensors that allow people to monitor how their blood is performing, as the sensors rely on understanding how proteins disrupt those surfaces.

Layers of fibrinogen grow thicker

For more than twenty years, the field has relied on a ‘single tilting layer’ model for fibrinogen where the long protein molecules lay flat on the surface at first and then leaned upright as more of them arrive.

The study, published in the Journal of the American Chemical Society, shows the benchmark model missed that fibrinogen stays lying flat and builds multiple layers that stack like sheets of paper. These layers grow thicker and more complete as more molecules arrive.

This new information helps to explain how the long protein molecules line up on the surface of blood where fibres called fibrin form the basis of the scab, a solid film formed during evaporation of fluid at the blood surface, that seals a wound.

Our findings may help scientists to understand better the behaviour of fibrinogen in the lungs of patients suffering from ARDS, a condition that tragically claimed so many lives during the pandemic.

“When the covid-19 pandemic struck, I spent time analysing structural data of how fibrinogen gathered at liquid surfaces while working from home. Then, after returning to work at the University, I applied additional experimental methods. It’s almost like we now have a full-circle moment, as our findings may help scientists to understand better the behaviour of fibrinogen in the lungs of patients suffering from ARDS, a condition that tragically claimed so many lives during the pandemic”, says Glenn Coope.

From the abstract:

“Layer-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.

Schematic of a scientific study. Illustration.

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 discussed 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 a wide range of bulk concentrations and at different ionic strengths. Our new findings 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, the enhanced competition for interfacial area from plasma proteins over phospholipids impairing lung function in patients with acute respiratory distress syndrome, and the strong innate immune recognition in nanoparticle protein coronas.”