Micromechanics of Red Blood Cells in Sickle Cell Disease

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In this project, the PI will model the entire healthy red blood cell (RBC) by introducing a coarse-grain molecular dynamics (CGMD) using a two-component membrane model for normal RBCs. The model will fully count for both the membrane skeleton and the phospholipid bilayer. The model will be expanded to simulate the entire healthy RBC. The characteristics of a quiescent healthy RBC, including its biconcave shape and material properties, will be obtained. In addition the PI will model sickle RBCs by creating a CGMD model for polymerized deoxygenated sickle hemoglobin (HbS) fibers and show how the interaction between HbS fibers and the membrane results to the biomechanical properties and to the variety of shapes of sickle RBCs via deformation, membrane loss and dehydration. The PI will also experimentally validate the model by employong AFM to measure local and average force displacement responses for normal and sickle RBCs from which the stiffness will be obtained. The average and local loss and storage moduli of normal and sickle RBCs will also be measured via active microrheology experiments. Simultaneously, the amount and the domains of polymerized HbS will be determined via an optical microscopy technique in the same cells where the mechanical properties are measured. The results of the CGMD simulations will be compared with the proposed single cell experiments to validate the model parameters. The outreach activities will promote engineering and science in high school teachers and students and in particular they will advance the participation of high school girls in science and technology. The educational program will promote the involvement of minority students in engineering and it will increase the interest of students in the multidisciplinary field of cell mechanics. The computational tools, the experimental setup, and the protocols will be available via a freely accessible website.