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.
| Savin, Thierry; Bandi, M M; Mahadevan, L (2016) Pressure-driven occlusive flow of a confined red blood cell. Soft Matter 12:562-73 |
| 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 |
