Neutrophil Chemotaxis in Moving Gradients

Abstract

Neutrophils are known to rapidly migrate to sites of infection and injury, and track bacteria guided by spatiotemporally controlled chemokine gradients. Previous studies of neutrophil chemotaxis, using micropipettes and lately microfluidic devices, are limited to stationary sources and gradients. Thus, despite the well‐known ability of neutrophils to track bacteria in vitro, their response to defined moving gradients remains unknown. Here, a “floating” concentration gradient of interleukin‐8 is generated using a microfluidic quadrupole, and neutrophils cultured in a Petri dish are challenged with steep stationary and moving gradients. Individual neutrophils are tracked by live microscopy and their chemotaxis is analyzed. Interestingly, neutrophils are shown to enter the gradient region in a rolling‐like behavior, rapidly adhere to the bare dish, and polarize within 30 s, faster than what has been observed to date. Under stationary gradients, neutrophil migration length is maximal for cells located at the low end of the gradient, whereas under moving gradients, neutrophils migrate over longer distances and the length travelled is independent of their starting position. Furthermore, neutrophils are shown to initiate their migration at a maximum speed, slowing down when migrating deeper into the gradient and eventually stopping. This work lays the foundation for future chemotaxis assays with moving gradients.

Microfluidic multipoles theory and applications

“…In the future, MFM devices may play an important role to study spatially resolved systems with fast transient kinetics. Using the presented advection-diffusion models, precise biochemical or thermal gradients can be generated, making MFM devices potentially useful to study biological processes sensitive to gradients, like neutrophils migration through chemotaxis 38 , stem cells differentiation 39 , and neuronal developement 40,41 .…”

Herringbone Microfluidic Probe for Multiplexed Affinity‐Capture of Prostate Circulating Tumor Cells

“…All these are desirable features considering the heterogeneous nature of CTCs; especially when the expression of surface proteins in CTCs vary greatly with their highly adaptive characteristics. [30] Nevertheless, since their first introduction, [31] the MFPs have already been deployed in several applications, such as cell stimulation [32] and manipulation. [33,34] More recently, we have developed 3D printing methodologies to manufacture MFPs with great modular capability in the design, [35,36] thus easing the implementation of new concepts and applications with simple design adjustments.…”

Operationalizing Goal Directedness: An Empirical Route to Advancing a Philosophical Discussion

“…Given this, a more meaningful question to ask is about the effect of starting distance on trajectory length. A similar approach that uses the ratio of the cell displacement toward the gradient to the total migration distance has been taken in the literature on chemotaxis, to calculate a "chemotaxis index" (e.g., McCutcheon 1946;Qasaimeh et al 2018).…”

“…Although called plasticity here for consistency with the philosophical literature, similar aspects of biological movements have been studied under such names as chemotaxis index (e.g., McCutcheon 1946;Qasaimeh et al 2018;Varennes et al 2019), and straightness index or navigation efficiency (Batschelet 1981;Benhamou and Bovet 1992;Benhamou 2004;Codling et al 2008;Bailey et al 2018;Benhamou et al 2003;Weimerskirch et al 2002), commonly measured as the ratio of net displacement to the total trajectory length. Often, such measures are employed to measure the tortuosity or convolutedness of movement path, which are thought to be key parameters in animal behaviors such as dispersal, foraging, and orientation (Benhamou 2004).…”