Gels of normal and sickled hemoglobin: comparative study

Area of Science:

• Biochemistry
• Hematology
• Structural Biology

Background:

• The sickling phenomenon in sickle cell disease is characterized by hemoglobin structural changes.
• Previous electron microscopy studies suggested multiple polymer structures, causing confusion about the molecular assembly mechanism.

Purpose of the Study:

• To determine the definitive structure of polymers formed by sickled hemoglobin.
• To clarify the mechanism of molecular assembly in sickle cell disease.

Main Methods:

• Formation of gels from cell-free solutions of normal and sickle hemoglobin under reduced and oxygenated conditions.
• Analysis of gel fine structure using electron microscopy.

Main Results:

• Gels of reduced sickled hemoglobin exclusively formed solid rods.
• Gels of sickle oxyhemoglobin, normal oxyhemoglobin, and normal reduced hemoglobin showed hollow polymers resembling microtubules.
• Microtubules were identified as aberrant structures, not related to erythrocyte sickling.

Conclusions:

• Solid rods represent the characteristic polymers of sickled hemoglobin.
• Hollow tubular polymers are not associated with the sickling process.
• This finding resolves discrepancies in understanding hemoglobin polymerization in sickle cell disease.