A Pillar-Free Diffusion Device for Studying Chemotaxis on Supported Lipid Bilayers

Chemotactic cell migration plays a crucial role in physiological and pathophysiological processes. In tissues, cells can migrate not only through extracellular matrix (ECM), but also along stromal cell surfaces via membrane-bound receptor–ligand interactions to fulfill critical functions. However, t...

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Main Authors: Jia Hao, Winfield Zhao, Jeong Min Oh, Keyue Shen
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Micromachines
Subjects:
Online Access:https://www.mdpi.com/2072-666X/12/10/1254
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author Jia Hao
Winfield Zhao
Jeong Min Oh
Keyue Shen
author_facet Jia Hao
Winfield Zhao
Jeong Min Oh
Keyue Shen
author_sort Jia Hao
collection DOAJ
description Chemotactic cell migration plays a crucial role in physiological and pathophysiological processes. In tissues, cells can migrate not only through extracellular matrix (ECM), but also along stromal cell surfaces via membrane-bound receptor–ligand interactions to fulfill critical functions. However, there remains a lack of models recapitulating chemotactic migration mediated through membrane-bound interactions. Here, using micro-milling, we engineered a multichannel diffusion device that incorporates a chemoattractant gradient and a supported lipid bilayer (SLB) tethered with membrane-bound factors that mimics stromal cell membranes. The chemoattractant channels are separated by hydrogel barriers from SLB in the cell loading channel, which enable precise control of timing and profile of the chemokine gradients applied on cells interacting with SLB. The hydrogel barriers are formed in pillar-free channels through a liquid pinning process, which eliminates complex cleanroom-based fabrications and distortion of chemoattractant gradient by pillars in typical microfluidic hydrogel barrier designs. As a proof-of-concept, we formed an SLB tethered with ICAM-1, and demonstrated its lateral mobility and different migratory behavior of Jurkat T cells on it from those on immobilized ICAM-1, under a gradient of chemokine CXCL12. Our platform can thus be widely used to investigate membrane-bound chemotaxis such as in cancer, immune, and stem cells.
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spelling doaj.art-6450cfceb0254b53a564705582827b642023-11-22T19:12:21ZengMDPI AGMicromachines2072-666X2021-10-011210125410.3390/mi12101254A Pillar-Free Diffusion Device for Studying Chemotaxis on Supported Lipid BilayersJia Hao0Winfield Zhao1Jeong Min Oh2Keyue Shen3Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USADepartment of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USADepartment of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USADepartment of Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USAChemotactic cell migration plays a crucial role in physiological and pathophysiological processes. In tissues, cells can migrate not only through extracellular matrix (ECM), but also along stromal cell surfaces via membrane-bound receptor–ligand interactions to fulfill critical functions. However, there remains a lack of models recapitulating chemotactic migration mediated through membrane-bound interactions. Here, using micro-milling, we engineered a multichannel diffusion device that incorporates a chemoattractant gradient and a supported lipid bilayer (SLB) tethered with membrane-bound factors that mimics stromal cell membranes. The chemoattractant channels are separated by hydrogel barriers from SLB in the cell loading channel, which enable precise control of timing and profile of the chemokine gradients applied on cells interacting with SLB. The hydrogel barriers are formed in pillar-free channels through a liquid pinning process, which eliminates complex cleanroom-based fabrications and distortion of chemoattractant gradient by pillars in typical microfluidic hydrogel barrier designs. As a proof-of-concept, we formed an SLB tethered with ICAM-1, and demonstrated its lateral mobility and different migratory behavior of Jurkat T cells on it from those on immobilized ICAM-1, under a gradient of chemokine CXCL12. Our platform can thus be widely used to investigate membrane-bound chemotaxis such as in cancer, immune, and stem cells.https://www.mdpi.com/2072-666X/12/10/1254chemotaxismicro-millingmicrodevicesupported lipid bilayermembrane-bound interactionsICAM-1
spellingShingle Jia Hao
Winfield Zhao
Jeong Min Oh
Keyue Shen
A Pillar-Free Diffusion Device for Studying Chemotaxis on Supported Lipid Bilayers
Micromachines
chemotaxis
micro-milling
microdevice
supported lipid bilayer
membrane-bound interactions
ICAM-1
title A Pillar-Free Diffusion Device for Studying Chemotaxis on Supported Lipid Bilayers
title_full A Pillar-Free Diffusion Device for Studying Chemotaxis on Supported Lipid Bilayers
title_fullStr A Pillar-Free Diffusion Device for Studying Chemotaxis on Supported Lipid Bilayers
title_full_unstemmed A Pillar-Free Diffusion Device for Studying Chemotaxis on Supported Lipid Bilayers
title_short A Pillar-Free Diffusion Device for Studying Chemotaxis on Supported Lipid Bilayers
title_sort pillar free diffusion device for studying chemotaxis on supported lipid bilayers
topic chemotaxis
micro-milling
microdevice
supported lipid bilayer
membrane-bound interactions
ICAM-1
url https://www.mdpi.com/2072-666X/12/10/1254
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AT winfieldzhao apillarfreediffusiondeviceforstudyingchemotaxisonsupportedlipidbilayers
AT jeongminoh apillarfreediffusiondeviceforstudyingchemotaxisonsupportedlipidbilayers
AT keyueshen apillarfreediffusiondeviceforstudyingchemotaxisonsupportedlipidbilayers
AT jiahao pillarfreediffusiondeviceforstudyingchemotaxisonsupportedlipidbilayers
AT winfieldzhao pillarfreediffusiondeviceforstudyingchemotaxisonsupportedlipidbilayers
AT jeongminoh pillarfreediffusiondeviceforstudyingchemotaxisonsupportedlipidbilayers
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