Sickle cell: from molecule to capillary
About this app
In HbS, position β6 carries valine instead of glutamate: without oxygen it locks into the pocket of the neighbouring molecule, HbS assembles after a delay time into fibres of 14 strands, and the red blood cell turns into a sickle that gets stuck in the capillary. Choose genotype AA, AS or SS and remove the O₂.
With explain mode: an AI tutor walks you through the app, points out what matters in the scene and answers your questions.
One base change, one sticky spot
In sickle cell anaemia, β-globin carries valine instead of glutamic acid at position 6 because a single base in the gene is changed (GAG to GTG). The hydrophobic valine fits into a pocket of the β chain of a neighbouring haemoglobin molecule. This pocket is only accessible when the haemoglobin carries no oxygen. Without oxygen, HbS molecules assemble after a delay time into long fibres of 14 strands. The fibres bend the red blood cell into a sickle; stiff sickle cells get stuck in narrow capillaries, and behind them the oxygen drops further.
What the app shows
Four views lead from the molecule to the vessel: two haemoglobin tetramers with Val6 and the pocket, fibre formation with a chart of the fibre share over time, the red blood cell with a micrometre scale, and blood flow through a 7.5 µm capillary with a narrowing. The genotype sets the HbS share: AA contains no HbS, AS about 40 %, SS about 90 %. The kinetic numbers come from a simplified model.
Things to try
Choose SS and remove the oxygen: fibres only grow after a short delay, then the cell sickles. Repeat with AS and compare the delay time with the time a cell needs to pass the capillary. Add oxygen again and raise the number of cycles until the cell stays deformed even with oxygen.
Frequently asked questions
- What happens to haemoglobin in sickle cell anaemia?
- In β-globin, position 6 carries valine instead of glutamic acid. Without oxygen the valine fits into a hydrophobic pocket of a neighbouring molecule. Many HbS molecules then assemble into fibres that deform the red blood cell and make it stiff.
- Why do carriers hardly suffer from sickle cell anaemia?
- Carriers (AS) have only about 40 % HbS. Fibre formation then starts only after a long delay, usually longer than the roughly one second a cell needs to pass a capillary. Their cells only sickle when oxygen is very low.
- Are sickle cells always sickle-shaped?
- No. The fibres form when oxygen is missing and dissolve again when the cell takes up oxygen. After many such cycles the membrane is damaged and some cells stay permanently deformed. Sickle cells live only 10 to 20 days instead of about 120.
- What can I set in the Sickle Cell app?
- You choose genotype AA, AS or SS, remove or add oxygen, follow fibre formation over time and set the number of oxygen cycles. Four views show molecule, fibre, cell and capillary.
Subject: Biology (Gymnasium)
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