Lighting up a critical biomolecule

A new procedure for detecting and quantifying a molecule in the blood called von Willebrand factor (vWF) offers several advantages over existing methods for monitoring its role in health and disease¹.

vWF is a glycoprotein molecule that is made and released by cells lining the inside of blood vessels, called endothelial cells, and also in bone marrow. It binds to a variety of other proteins and cells to regulate biochemical processes that keep the body’s systems operating normally and able to respond to injury. Notably, its role in assisting blood clotting is behind the symptom of excess bleeding in von Willebrand disease – an inherited genetic deficiency of vWF.

In a study published in the journal Biochemistry (Moscow), a research team based at the Koltsov Institute of Developmental Biology in Moscow has now developed a quantitative test for vWF by attaching a fluorescent chemical group to a molecule called an aptamer, which selectively binds to vWF. This allows the abundance of vWF to be monitored by measuring the fluorescence produced by the bound aptamer.

“Our technique seems likely to improve on existing methods through improved sensitivity and specificity, as well as increased speed at reduced cost,” says Pavel Avdonin from the research team.

Avdonin points out that existing methods can artificially increase the release of vWF from the endothelial cell samples being tested, making it difficult to accurately interpret the relevance of the results obtained. The new method overcomes his drawback.

While the researchers were developing their technique, the emergence of the COVID-19 pandemic revealed a surprising new significance of the need for accurate, fast and cost-effective methods to test for vWF. The body’s inflammatory response during COVID -19, which causes much of the damage associated with the disease, initiates increased release of vWF with effects that disrupt the healthy balance of the body’s biochemical systems.

“We thought we were working on a long-term issue, but we suddenly realized that COVID-19 gave it immediate importance,” says Avdonin.

In their current research paper, the power of the technique is demonstrated by using it to quantify the release of vWF by human umbilical vein endothelial cells. This work also revealed that the chemical hydrogen peroxide, which occurs naturally in the body, can act to stimulate the release of vWF.

As the approach is based on an aptamer, which is an oligonucleotide similar in structure to DNA, Avdonin hopes that different aptamers could be used to adapt the technique to quantify many other biomolecules.