The City College of New YorkCCNY
Department of Mathematics
Division of Science

Multi-Scale and Multi-Physics Modeling of Proteins and Cells – A Computational Protocol for Complex Systems

Mathematics Colloquium

Time and place

1 PM on Tuesday, March 24th, 2009; NAC 4/113

Dr. X. Sheldon Wang (New Jersey Institute of Technology)

Abstract

Sickle cell anemia is one of the first diseases pinpointed to the genetic cause at the DNA level. Hemoglobin in its quaternary molecular structure is very much like a bead. The red blood cell has many such beads within the cell cytoskeleton. The cause of the sickle cell disease is a simple switch of the DNA base pair from A to T, with this switch, the codon will be changed from GAG to GTG. The normal hemoglobin at this particular location is slightly hydrophilic, thus tends to form a protective layer with the surrounding water molecules and is separated from each other. As a consequence, the normal red blood cell membrane is flexible and fluidic. Due to the sickle cell mutation, the hydrophilic spot becomes slightly hydrophobic and during the deoxygenated state, it tends to loose the protective layer of water molecules and consequently forms a chain of hemoglobin beads. Moreover, such chains will continue to form bundles and eventually yield a very stiff and sticky material property for the sickle cell membrane. In the end, these sickle cells tend to block the capillary vessels and cause the sickle cell anemia. In this research, we will use this well-established system as an example to explore a multi-scale and multi-physics modeling procedure for biological systems. We start with a series of molecular dynamics simulations of hemoglobin-hemoglobin interactions coupled with surrounding water molecules. Different level of coarse graining models will be employed to establish the likelihood of forming hemoglobin chains under difference circumstances. Simplified models of hemoglobin immersed in aqueous environment will be introduced in immersed boundary/continuum methods for the direct simulation of phase transitions of normal and sickle red blood cell membranes. Ultimately, cells modeled as soft continua will be coupled with viscous fluid in microcirculations. We hope that mathematical tools such as singular value decomposition, principal component analysis, coupled solution algorithm based on matrix-free Newton-Krylov iterative procedures introduced for such a complex fluid-solid system will help to establish a computational protocol for complex dynamical systems.

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