The pathophysiology of sickle cell disease, the first to be implicated with a genetic origin, is complicated by the multi-scale nature of the processes that link the molecular genotype to the organismal phenotype. The investigators propose to evoke, control and inhibit the vaso-occlusive crisis event in sickle cell disease using an artificial microfluidic environment. They will use a combination of geometric, physical, chemical and biological means to quantify the phase space for the onset of a jamming crisis, as well as its dissolution. They will also investigate the role of small molecule inhibitors and the effects of therapeutic red blood cell exchange on this dynamical process. This experimental study will integrate the dynamics of collective processes at the molecular, polymer, cellular and multi-cellular level, lay the foundation for a quantitative understanding of the rate limiting processes, and provide a potential tool for optimizing and individualizing treatment and serves as a test bench for dynamical drugs. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL091331-01
Application #
7361435
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Luksenburg, Harvey
Project Start
2007-12-01
Project End
2009-11-30
Budget Start
2007-12-01
Budget End
2008-11-30
Support Year
1
Fiscal Year
2008
Total Cost
$231,950
Indirect Cost
Name
Harvard University
Department
Engineering (All Types)
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
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Mani, Madhav; Gopinath, Arvind; Mahadevan, L (2012) How things get stuck: kinetics, elastohydrodynamics, and soft adhesion. Phys Rev Lett 108:226104
Higgins, John M; Mahadevan, L (2010) Physiological and pathological population dynamics of circulating human red blood cells. Proc Natl Acad Sci U S A 107:20587-92
Higgins, John M; Eddington, David T; Bhatia, Sangeeta N et al. (2009) Statistical dynamics of flowing red blood cells by morphological image processing. PLoS Comput Biol 5:e1000288
Charras, Guillaume T; Mitchison, Timothy J; Mahadevan, L (2009) Animal cell hydraulics. J Cell Sci 122:3233-41