This project addresses the effect of point mutations on the structure of hemoglobin S fibers and fiber networks. The proposed elements have three principal foci: (1) the interactions between fibers which are responsible for heterogenous nucleation and fiber cross-linking; (2) the effect of components of the red cell on these fundamental processes and (3) the detailed characterization of the kinetics of fiber and gel melting. Differential interference contrast (DIC) light microscopy, pioneered by Dr. Briehl, will also be used to examine the polymerization and depolymerization of mutant hemoglobins. Photolysis of carbon monoxide will be used as the primary technique to prepare polymerizing samples and to control the rate of polymerization and melting. Other techniques such as determination of c(sat) and the more conventional methods for measuring polymerization progress curves, such as light scattering, will be used to supplement the DCI technique.
| Yosmanovich, Donna; Rotter, Maria; Aprelev, Alexey et al. (2016) Calibrating Sickle Cell Disease. J Mol Biol 428:1506-14 |
| Tokarev, Alexander; Aprelev, Alexey; Zakharov, Mikhail N et al. (2012) Multifunctional magnetic rotator for micro and nanorheological studies. Rev Sci Instrum 83:065110 |
| Manning, James M; Popowicz, Anthony M; Padovan, Julio C et al. (2012) Intrinsic regulation of hemoglobin expression by variable subunit interface strengths. FEBS J 279:361-9 |
| Weng, Weijun; Ferrone, Frank A (2011) Metastable gels: A novel application of Ogston theory to sickle hemoglobin polymers. Biophys Chem 154:99-101 |
| Rotter, Maria; Yosmanovich, Donna; Briehl, Robin W et al. (2011) Nucleation of sickle hemoglobin mixed with hemoglobin A: experimental and theoretical studies of hybrid-forming mixtures. Biophys J 101:2790-7 |
| Rotter, Maria A; Chu, Haiyan; Low, Philip S et al. (2010) Band 3 catalyzes sickle hemoglobin polymerization. Biophys Chem 146:55-9 |
| Zakharov, Mikhail N; Aprelev, Alexey; Turner, Matthew S et al. (2010) The microrheology of sickle hemoglobin gels. Biophys J 99:1149-56 |
| Manning, Lois R; Popowicz, Anthony M; Padovan, Julio et al. (2010) Developmental expression of human hemoglobins mediated by maturation of their subunit interfaces. Protein Sci 19:1595-9 |
| Wang, Jiang Cheng; Kwong, Suzanna; Ferrone, Frank A et al. (2009) Fiber depolymerization: fracture, fragments, vanishing times, and stochastics in sickle hemoglobin. Biophys J 96:655-70 |
| Manning, Lois R; Russell, J Eric; Popowicz, Anthony M et al. (2009) Energetic differences at the subunit interfaces of normal human hemoglobins correlate with their developmental profile. Biochemistry 48:7568-74 |
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