The Vroman effect, named after Leo Vroman, describes the process of competitive protein adsorption to a surface by blood serum proteins. The highest mobility proteins generally arrive first and are later replaced by less mobile proteins that have a higher affinity for the surface. The order of protein adsorption also depends on the molecular weight of the species adsorbing. Typically, low molecular weight proteins are displaced by high molecular weight protein while the opposite, high molecular weight being displaced by low molecular weight, does not occur. A typical example of this occurs when fibrinogen displaces earlier adsorbed proteins on a biopolymer surface and is later replaced by high molecular weight kininogen. The process is delayed in narrow spaces and on hydrophobic surfaces, fibrinogen is usually not displaced. Under stagnant conditions initial protein deposition takes place in the sequence:

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...

;

globulin The globulins are a family of globular proteins that have higher molecular weights than albumins and are insoluble in pure water but dissolve in dilute salt solutions. Some globulins are produced in the liver, while others are made by the immune ...

;

fibrinogen Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood cl ...

;

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...

;

factor XII Coagulation factor XII, also known as Hageman factor, is a plasma protein. It is the zymogen form of factor XIIa, an enzyme () of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by the ''F12'' gene. Struc ...

, and HMWK.

Molecular Mechanisms of Action

While the exact mechanism of action is still unknown many important protein physical properties play a part in the Vroman Effect.

Protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s have many properties that are important to take into consideration when discussing protein adsorption. These properties include the protein size, charge, mobility, stability, and the structure and composition of the different

protein domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of ...

s that make up the protein's

tertiary structure Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may i ...

. Protein size determines the molecular weight. Protein charge determines whether preferentially or selective favorable interactions will exist between the protein and a biomaterial. Protein mobility plays a factor in adsorption kinetics.

Adsorption - Desorption Model

The simplest molecular explanation for the exchange of proteins on a surface is the

adsorption Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which ...

desorption Desorption is the physical process where a previously adsorbed substance is released from a surface. This happens when a molecule gains enough energy to overcome the activation barrier of the bounding energy that keeps it in the surface. There ...

model. Here, proteins interact with the surface of a biomaterial and "stick" on the material through interactions made with the protein and the biomaterial surface. Once a protein has adsorbed onto the surface of a biomaterial, the protein may change conformation (structure) and even become nonfunctional. The spaces between the proteins on the biomaterial then become available for new proteins to adsorb. Desorption occurs when the protein leaves the biomaterial surface. This simple model lacks in complexity, since Vroman-like behavior has been observed on hydrophobic surfaces as well as hydrophilic ones. Furthermore, adsorption and desorption doesn't completely explain competitive protein exchange on hydrophilic surfaces.

Transient Complex Model

A "transient complex" model was first proposed by Huetz et al. to explain this competitive exchange. This transient complex exchange occurs in three distinct steps. Initially a protein embeds itself into the monolayer of an already adsorbed homogenous protein monolayer. The aggregation of this new heterogenous protein mixture causes the "turning" of the double-protein complex which exposes the initially adsorbed protein to the solution. In the third step, the protein that was initially adsorbed can now diffuse out into the solution and the new protein takes over. This 3 part "transient complex mechanism" is further explained and verified through AFM imaging by Hirsh et al.

pH Cycling

Jung et al. also describe a molecular mechanism for fibrinogen displacement involving pH cycling. Here the αC domains of fibrinogen change charge after pH cycling which results in conformational changes to the protein that leads to stronger interactions with the protein and the biomaterial.

Mathematical Models

The simplest mathematical model to explain the Vroman Effect is the Langmuir model using the Langmuir isotherm. More complex models include the Fruendlich isotherm and other modifications to the Langmuir model. This model explains the kinetics between reversible adsorption and desorption, assuming the

adsorbate Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which a f ...

behaves as an

ideal gas An ideal gas is a theoretical gas composed of many randomly moving point particles that are not subject to interparticle interactions. The ideal gas concept is useful because it obeys the ideal gas law, a simplified equation of state, and is a ...

isothermal In thermodynamics, an isothermal process is a type of thermodynamic process in which the temperature ''T'' of a system remains constant: Δ''T'' = 0. This typically occurs when a system is in contact with an outside thermal reservoir, and ...

conditions.

References