Microfluidic Modeling of Circulating Leukocyte Deformation

Abstract

Acute lung injury (ALI) and its presentation with more severe hypoxemia, the Acute Respiratory Distress Syndrome (ARDS), is a potentially fatal disease which lacks an accepted diagnostic test and relies on a constellation of clinical findings for diagnosis. Alterations of microvascular blood flow is associated with acquired rigidity of white blood cells (WBCs) and capillary blockage. Measuring leukocyte deformation and transit process in vivo is a difficult task and thus in vitro techniques have played an important role in modeling cell deformability, especially by yielding information on the first step of leukocyte entry into capillaries. However, after many attempts done at quantifying leukocyte rheology, recent observations highlight our lack of knowledge of the precise role of the cytoskeletal rearrangements on the control of circulating leukocyte deformability. In this article, we demonstrate the unique abilities and benefits of microfluidics to characterize complex mechanical behaviors of single WBCs, under physiological flow, in narrow capillary. Deformation of leukocytes were evaluated using elastomeric microchannels by mimicking the flow conditions within lung capillaries to study cytoskeletal changes for their influences on the overall mechanical behavior, as a function of a large range of pressure drops. We present results suggesting a specific role for cytoskeletal remodeling (through actin polymerization-depolymerization) to allow cells to enter channels, and tension (trough actin-myosin interaction) to limit overall deformation. Being a valuable tool for rapid quantification of cell deformability, microfluidic devices also provide a convenient test platform to screen potential drugs that specifically interfere with the leukocyte stiffness of ARDS patients.