A fibrin biofilm covers blood clots and protects from microbial invasion

Abstract

Hemostasis requires conversion of fibrinogen to fibrin fibers that generate a characteristic network, interact with blood cells, and initiate tissue repair. The fibrin network is porous and highly permeable, but the spatial arrangement of the external clot face is unknown. Here we show that fibrin transitioned to the blood-air interface through Langmuir film formation, producing a protective film confining clots in human and mouse models. We demonstrated that only fibrin is required for formation of the film, and that it occurred in vitro and in vivo. The fibrin film connected to the underlying clot network through tethering fibers. It was digested by plasmin, and formation of the film was prevented with surfactants. Functionally, the film retained blood cells and protected against penetration by bacterial pathogens in a murine model of dermal infection. Our data show a remarkable aspect of blood clotting in which fibrin forms a protective film covering the external surface of the clot, defending the organism against microbial invasion.

Topical tranexamic acid inhibits fibrinolysis more effectively when formulated with self‐propelling particles

“…Because gas‐liquid interfaces aggregate proteins and stimulate coagulation, a control experiment was performed to measure the effects of CO 2 generation on clot initiation and fibrinolysis in this model, using self‐propelling particles containing a pharmacologically inert acid that generated CO 2 but did not contain TXA. Recalcified normal human plasma (400 μL) containing 150 ng/mL tissue‐type plasminogen activator (Activase/alteplase; Genentech) was drawn into a 1.0‐mL serological pipet.…”

“…Plasma was chosen, rather than whole blood, because it contains the primary fibrinolytic components and lyses more consistently. Plasma Because gas-liquid interfaces aggregate proteins and stimulate coagulation, 26,27 a control experiment was performed to measure the effects of CO 2 generation on clot initiation and fibrinolysis in this model, using self-propelling particles containing a pharmacologically inert acid that generated CO 2 but did not contain TXA.…”

Keeping it clean: clot biofilm to wall out bacterial invasion

“…Fibrin and fibrinogen form a thin film at the liquid–air interface during the process of clot formation . Rather than being a typical porous network of fibers, these films appear to be made up of tightly packed molecules arranged perpendicular to the liquid–air interface tethered to the underlining polymeric fibrin network.…”

“…In a general context, the work by Macrae et al . studies a molecular mechanism of spatial biological partitioning that may occur without formation of phospholipid membranes, perhaps similarly to assembly of some membrane‐less cellular organelles. Irrespective of the underlying mechanisms, formation of a proteinaceous film surrounding a blood clot can be considered as an example of biological compartmentalization, a structural and functional biological principle now applied to the extracellular matrix.…”

“…The recent report of fibrin biofilms at the liquid–air interface of fibrin clots provides another mechanism for antimicrobial protection . Although the discovery of these fibrin biofilms may appear unexpected, their existence on the surface of in vitro clots has been known for quite some time.…”