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

Yongjun Choi,Yoon-Kyoung Cho,Jae-Eun Kwon

doi:10.3390/cells10123362

Yongjun Choi, Yoon-Kyoung Cho + Show 1 more

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https://doi.org/10.3390/cells10123362

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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.

Highlights

Dendritic cells (DCs) patrol the tissue microenvironment, acting as immune sentinels to search for and phagocytose pathogens
We found that cell height was distinctively increased at low mechanical load (1.2 kPa) (Figure 1D)
2D trajectories of the cells migrating under gels with difdiffusion trajectories of the cells migrating under gels with different ferent stiffnesses, we examined multiple statistical functions, including mean square displacement (MSD), autocorrelation function of the velocities (ACF), and stiffnesses, wedistribution, examined multiple functions, ACF,we andobtained turning turning angle using astatistical previously reportedincluding protocol MSD

Summary

Introduction

Dendritic cells (DCs) patrol the tissue microenvironment, acting as immune sentinels to search for and phagocytose pathogens. Since this surveillance by immature DCs is the basis of the innate immune response, it is crucial to understand the physical and biochemical factors that influence it. Previous studies have demonstrated that DC motility is modulated by external factors including cytokines [1,2], pathogen components [3,4,5], and ATP released from dead cells [6]. Recent studies suggest that mechanical and geometrical cues, including confinement, rigidity, topology, and porosity of the microenvironment, modulate DC motility [7,8] and function [9]. Haptotaxis—directional motility guided by an adhesion molecular gradient—was suggested by a study using a microfabricated

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