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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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Autores principales: Hao, Jia, Zhao, Winfield, Oh, Jeong Min, Shen, Keyue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538285/
https://www.ncbi.nlm.nih.gov/pubmed/34683305
http://dx.doi.org/10.3390/mi12101254
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author Hao, Jia
Zhao, Winfield
Oh, Jeong Min
Shen, Keyue
author_facet Hao, Jia
Zhao, Winfield
Oh, Jeong Min
Shen, Keyue
author_sort Hao, Jia
collection PubMed
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 pubmed-85382852021-10-24 A Pillar-Free Diffusion Device for Studying Chemotaxis on Supported Lipid Bilayers Hao, Jia Zhao, Winfield Oh, Jeong Min Shen, Keyue Micromachines (Basel) Article 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. MDPI 2021-10-16 /pmc/articles/PMC8538285/ /pubmed/34683305 http://dx.doi.org/10.3390/mi12101254 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hao, Jia
Zhao, Winfield
Oh, Jeong Min
Shen, Keyue
A Pillar-Free Diffusion Device for Studying Chemotaxis on Supported Lipid Bilayers
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538285/
https://www.ncbi.nlm.nih.gov/pubmed/34683305
http://dx.doi.org/10.3390/mi12101254
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