Dendritic Cell Migration Is Tuned by Mechanical Stiffness of the Confining Space

Abstract

The coordination of cell migration of immune cells is a critical aspect of the immune response to pathogens. Dendritic cells (DCs), the sentinels of the immune system, are exposed to complex tissue microenvironments with a wide range of stiffnesses. Recent studies have revealed the importance of mechanical cues in immune cell trafficking in confined 3D environments. However, the mechanism by which stiffness modulates the intrinsic motility of immature DCs remains poorly understood. Here, immature DCs were found to navigate confined spaces in a rapid and persistent manner, surveying a wide range when covered with compliant gels mimicking soft tissues. However, the speed and persistence time of random motility were both decreased by confinement in gels with higher stiffness, mimicking skin or diseased, fibrotic tissue. The impact of stiffness of surrounding tissue is crucial because most in vitro studies to date have been based on cellular locomotion when confined by microfabricated polydimethylsiloxane structures. Our study provides evidence for a role for environmental mechanical stiffness in the surveillance strategy of immature DCs in tissues.

Microfluidic Lab-on-a-Chip for Studies of Cell Migration under Spatial Confinement

“…In this way, it is possible to inject the biological sample in the central channel and observe the chemotaxis-induced migration, avoiding liquid media exchange between the various compartments of the device. Choi et al [ 63 ] exploited the tunable mechanical properties of agarose to fabricate a gel confiner device with different stiffness, as shown in Figure 4 a. This device consists of a hydrogel lid that is placed on the top of some 2D seeded cells in order to apply on them a known pressure and study their migration once confined.…”

“… Examples of microfluidic migration assays realized with hydrogels:( a ) Hydrogel lid used to apply controlled mechanical load on migrating cells (Reprinted with permission from Ref. [ 63 ] Copyright 2021, Choi et al); ( b ) Microchannels array with different size and stiffness realized exploiting hydrogel mechanical–chemical properties (Reprinted with permission from Ref. [ 64 ].…”

The T Cell Journey: A Tour de Force

“…Cells, specifically APCs, exhibit diverse phenotypic states [87][88][89] that are instructed by external biophysical cues. [90][91][92][93] Phenotypic states include biomechanical properties such as cell's stiffness, which has been used as a parameter to differentiate between healthy and diseased cells. [94,95] Hence, evaluation of single cell biomechanical properties has become imperative to understand ensuing cell response.…”

Study of Cell Migration under Mechanical Confinement in Microfluidic Lab-on-a-Chip

“…The peculiarity of this device is that the three channels are not connected and the chemical gradient is established through the hydrogel matrix, leading to a linear chemical diffusion without liquid media exchange. Choi et al [55] exploited the tunable mechanical properties of agarose to fabricate a gel confiner device with different stiffness, as shown in Figure 4.b . This device consists in a hydrogel lid that is placed on the top of some 2D seeded cells in order to apply on them a known pressure and study their migration once confined.…”