The research objective of this award is to characterize at the single molecule level the interactions between erythrocyte adhesion receptors and their corresponding ligands, and to measure the effect of agonist activation signaling on the strength and the frequency of adhesion events. The findings will be correlated with ex vivo adhesion of intact erythrocytes to adhesive ligands under conditions of flow. Traditionally, erythrocytes were considered to be inert cells containing hemoglobin and functioning only as oxygen carriers. Recently, it has been found that erythrocytes express an unexpected number of adhesion receptors on their surfaces and we begin to understand that external stimuli, such as adrenergic hormones, increase the ability of even mature erythrocytes to adhere. Atomic force microscopy combined with microfluidics will be used to carry out the measurements while multiscale numerical simulations will be employed to correlate single molecule experimental results with overall RBC adhesion experiments.
The proposed research will answer very fundamental questions related to erythrocyte adhesion. It is expected to identify which of the RBC receptors are related to higher strength and increased frequency of adhesion events and how external signaling modifies RBC adhesion at the molecular level and in physiological blood flow conditions. The results are expected to have a very important positive impact because the identified adhesion receptors and mechanisms are very likely to provide new pharmacological targets and therapeutic approaches for the prevention and treatment of peripheral vascular diseases. The educational plan will result in the development of a series of interdisciplinary graduate courses on Cell Mechanics at UConn, Storrs. It will also promote engineering and science in high school teachers and students. In particular, it will advance the participation of 9th to 11th grade girls from a local high school in science and technology.
