Natural killer cell migration control in microchannels by perturbations and topography
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Published on: January 9, 2018
1Department of Electronic Engineering, Center for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Hong Kong. pang@cityu.edu.hk.
Abstract:
Natural killer (NK) cells are lymphocytes which play an important role in the immune system by recognizing and killing potentially malignant cells without antigen sensitization, and could be utilized in cancer therapy. NK cell migration is an essential process to find and kill target cells, which is well known to be driven by the chemotaxis effect. NK cells also experience a topographical effect induced by the extracellular matrix (ECM) during their migration. However, topographical effects on NK cell locomotion in three dimensional (3D) environments are not well studied yet. In this work, polydimethylsiloxane based platforms containing microchannels with different types of perturbations and decorated with various surface patterns were fabricated to systematically study the topographical effect on NK cell migration with and without the chemotaxis effect. The results showed that perturbation sites in channels induced pauses and reversals in chemotaxis driven NK cell migration. Surface topography such as gratings in confined environments could introduce directional preference to NK cell movement even without chemoattractants. These findings showed that NK cell migration could be controlled by contact guidance, which provides future possibility to manipulate NK cell migration in controlled in vitro bioengineering systems. Results in this study showed that the complex topography of 3D microenvironments in the ECM could have significant effects on NK cell migration in different tissues and organs, and provided insight for explaining the dynamics of NK cell activities in clinical experiments.
Insights
Natural killer (NK) cell migration is influenced by physical cues. Microchannel topography can control NK cell movement, offering new ways to guide these immune cells for cancer therapy.
Area of Science:
- Immunology
- Biomaterials Science
- Cell Biology
Background:
- Natural killer (NK) cells are crucial lymphocytes for innate immunity and cancer surveillance.
- NK cell migration, essential for targeting malignant cells, is primarily driven by chemotaxis.
- The influence of topographical cues from the extracellular matrix (ECM) on NK cell locomotion in 3D environments remains underexplored.
Purpose of the Study:
- To systematically investigate the topographical effects on NK cell migration in 3D microenvironments.
- To examine how microchannel perturbations and surface patterns influence NK cell movement with and without chemotaxis.
- To explore the potential of contact guidance for controlling NK cell migration in bioengineering systems.
Main Methods:
- Fabrication of polydimethylsiloxane (PDMS) based microfluidic platforms with varied channel perturbations and surface patterns.
- Systematic observation and analysis of NK cell migration dynamics under different topographical conditions.
- Integration of chemotaxis stimuli to study combined topographical and chemical guidance effects.
Main Results:
- Microchannel perturbations induced pauses and reversals in chemotaxis-driven NK cell migration.
- Surface topography, like gratings, provided directional preference for NK cell movement even in the absence of chemoattractants.
- Contact guidance was demonstrated as a significant factor influencing NK cell locomotion.
Conclusions:
- NK cell migration is significantly modulated by the physical topography of their 3D microenvironment.
- Engineered topographical cues can control NK cell movement, presenting opportunities for in vitro bioengineering applications.
- Findings offer insights into NK cell dynamics in complex biological tissues and potential applications in cancer immunotherapy.
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