Linking structure to mechanics: Modelling cell deformation under flow
Cells within the blood have widely varying mechanical properties, not only dependent on the cell type, but also on the age and health of the cell. To illustrate, the mechanical properties of red blood cells (RBCs or erythrocytes) are dominated by their area-conserving viscous phospholipid membrane, and to a lesser extent, by their internal elastic spectrin cytoskeleton that is tethered to this membrane. In a healthy RBC the properties of the RBC's cytoplasm (roughly Newtonian, with a viscosity approximately 5 times that of the surrounding plasma) are relatively unimportant in determining the cell's mechanical behaviour. However, in diseased states such as sickle cell anemia, diabetes mellitus and malignant malaria, RBCs show greatly reduced deformation, implying that viscoelastic cytoplasm and cytoskeleton properties become more important. Leukocytes (White Blood Cells or WBCs) are also surrounded by a viscous membrane, but in these cells the cytosketal network is stronger than RBCs, resulting in a cell that deforms less and (in general) more elastically. Like RBCs, in diseased states the physical properties of WBCs change. For example, neutrophils in patients with sepsis, septic shock and adult respiratory distress deform less due to increased actin (cytoskeleton) polymerisation. To be useful in a diagnosis or design setting, cell models for predicting cell deformation and flow behaviour need to be able to link cell structure to cell mechanics, and to be able to cope with a wide spectrum of cell materials.
Within this PhD project we will develop a cell model based on the viscoelastic Navier-Stokes equations, capable of resolving the viscoelastic behaviour of the cytoplasm, combined with a diffuse interface method for modelling both the elastic strains (extensional for areal expansion and shear) and viscous shear stress within a membrane interface. Having this model we will be able to: a) model all blood cell types using a single consistent approach, allowing cell deformation and flow to be predicted as a function of material structure; and b) probe, via shape analysis and flow behaviour, how disease affects the underlying mechanical properties of each cell type, not limiting ourselves to (healthy) cells that are either dominated entirely by membrane or cytoplasmic forces.
Leader: Dalton Harvie
Biomedical Engineering,Chemical & Biomolecular Engineering
Convergence of engineering and IT with the life sciences
Complex Fluids; computational biology; fluid dynamics; fluid mechanics