Experimental and theoretical multiscale model of sickle cell vaso-occlusion in a

描述（由申请人提供）：镰状细胞病的病理生理学是第一个与遗传起源有关的疾病，由于将分子基因型与生物体表型联系起来的过程的多尺度性质而变得复杂。研究人员建议使用人工微流体环境来诱发、控制和抑制镰状细胞病中的血管闭塞危象事件。他们将使用几何，物理，化学和生物手段的组合来量化干扰危机开始的相空间，以及它的溶解。他们还将研究小分子抑制剂的作用以及治疗性红细胞交换对这一动态过程的影响。本实验研究将整合在分子，聚合物，细胞和多细胞水平上的集体过程的动力学，奠定了定量理解的限速过程的基础，并提供了一个潜在的工具，优化和个性化治疗，并作为一个测试平台的动态药物。

DESCRIPTION (provided by applicant): 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.