The unique ability of the red blood cell to deform and withstand the high shear stress in the circulation is lost with altered molecular interactions in te membrane or changes in the cytosol. We have developed a novel technique "Single Cell Micro-chamber Array" or SiCMA, to rapidly analyze heterogeneous cell populations, and plan to show that this technology will allow the correlation of deformation and fragility with cell surface and cytosolic markers in heterogeneous populations of red blood cells. We propose a multidisciplinary approach with experts from mechanical engineering, cell biology, and clinical hematology to develop a novel technology for red cell membrane biology and show its applicability for clinical diagnosis of patients with hereditary spherocytosis (HS). To reach this goal we have formulated the following specific aims: 1) To optimize deformation measurements in SiCMA chambers, 2) To compare SiCMA deformation analysis with established technology, and 3.) To test the new technology on samples relevant for red cell pathology. Successful accomplishment will lead to the establishment of a novel approach to rapidly and highly cost-effective, select, define, and correlate cellular markers of individual cells in a heterogeneous re cell population, to be used in laboratory assessment of basic research in membrane biology as well as for prognosis and treatment of red cell disorders.

Public Health Relevance

The unique ability of the red blood cell to deform and withstand the high shear stress in the circulation is lost with altered molecular interactions in te membrane or changes in the cytosol. Laboratory measurements of red cell to deformability provide the average deformation of a large population of red cells, or can determine this in limited numbers of individual red cells. We propose a multidisciplinary approach with experts from mechanical engineering, cell biology, and clinical hematology to develop a novel technology that will allow the determination of deformability and fragility of individual cells in large populations of red cells, and correlate deformation with both membrane and cytosolic markers. Successful completion of this project will provide a better assessment of heterogeneous red cell populations, important for cell biology and clinical diagnosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL113490-01A1
Application #
8446105
Study Section
Molecular and Cellular Hematology (MCH)
Program Officer
Hanspal, Manjit
Project Start
2013-01-18
Project End
2014-12-31
Budget Start
2013-01-18
Budget End
2013-12-31
Support Year
1
Fiscal Year
2013
Total Cost
$245,250
Indirect Cost
$95,250
Name
Children's Hospital & Res Ctr at Oakland
Department
Type
DUNS #
076536184
City
Oakland
State
CA
Country
United States
Zip Code
94609