Computer models developed by Brown University mathematicians, including Lu Lu, an Applied Mathematics doctoral student, show new details of what happens inside a red blood cell affected by sickle cell disease. The researchers said they hope their models, described in an article in the Biophysical Journal, will help in assessing drug strategies to combat the genetic blood disorder, which affects millions of people worldwide.
Sickle cell disease affects hemoglobin, molecules within red blood cells responsible for transporting oxygen. In normal red blood cells, hemoglobin is dispersed evenly throughout the cell. In sickle red blood cells, mutated hemoglobin can polymerize when deprived of oxygen, assembling themselves into long polymer fibers that push against the membranes of the cells, forcing them out of shape. The stiff, ill-shaped cells can become lodged in small capillaries throughout the body, leading to painful episodes known as sickle cell crisis.
“The goal of our work is to model both how these sickle hemoglobin fibers form as well as the mechanical properties of those fibers,” said Lu who is the study’s lead author. “There had been separate models for each of these things individually developed by us, but this brings those together into one comprehensive model.”
The model uses detailed biomechanical data on how sickle hemoglobin molecules behave and bind with each other to simulate the assembly of a polymer fiber. Prior to this work, the problem had been that as the fiber grows, so does the amount of data the model must crunch. Modeling an entire polymer fiber at cellular scale using the details of each molecule was simply too computationally expensive.
Read more of Kevin Stacey's story on computer models of sickle cell disease.