Healthy red blood cells are soft and are not sticky so that they can slip easily through even the narrowest of blood vessels in the body. Increased stiffness and stickiness of red blood cells can impair blood circulation and this does occur in many diseases and conditions, including anemias, sepsis, malaria, lupus, heavy metal poisoning, blood transfusion complications, diabetes, cancer, kidney and cardiovascular diseases, obesity, and some neurological disorders. Medicine does not have a complete understanding of the mechanical changes of red blood cells in these conditions. This Faculty Early Career Development (CAREER) project will advance our knowledge of red blood cell adhesion and deformability in the microcirculation using special built micro-channel devices that have adjustable stickiness where one can see the deformation of the cells as they flow, deform and interact with the micro-vessel walls. The principal investigator will use the beautiful imagery and the scientific art that arises from these experiments to reach out to the community through the Science, Technology and Art (STArt) education program that will be developed in collaboration with the Cleveland Institute of Art. The STArt program aims to stimulate scientific curiosity and interest in high school students through hands-on, scientific art themed workshops.
The research objective of this CAREER award is to test the hypothesis that a red blood cell's adhesion affinity is a function of its deformability and phosphatidylserine translocation to the outer membrane surface. The exceptional deformability of the red blood cell is facilitated by its membrane skeleton, which is physically connected to the adhesion receptors. Phosphatidylserine is a phospholipid located on the inner leaflet of the cell membrane. Even though the translocation of phosphatidylserine to the outer membrane surface has been correlated to adhesion, its role in red blood cell's increased adhesion affinity remains unclear. The research will systematically investigate, at the single cell level, the biomechanical properties of live red blood cells in microphysiological blood flow. The new knowledge gained will answer important questions: (1) which of the red blood cell receptors are associated with higher adhesion affinity and lower deformability? (2) Is the adhesion affinity a surrogate measure of red blood cell's deformability, phosphatidylserine translocation, and function? (3) Can the unhealthy red blood cells be identified and excluded from the circulation solely based on their adhesion affinity and reduced deformability? Proposed research will pioneer an integrated understanding of red blood cell adhesion and deformability, which may be pertinent to any disease accompanied by microcirculatory impairment.
