Deterministic Single Cell Encapsulation in Asymmetric Microenvironments to Direct Cell Polarity

Deterministic Single Cell Encapsulation in Asymmetric Microenvironments to Direct Cell Polarity

Various signals in tissue microenvironments are often unevenly distributed around cells. Cellular responses to asymmetric cell‐matrix adhesion in a 3D space remain generally unclear and are to be studied at the single‐cell resolution. Here, the authors developed a droplet‐based microfluidic approach...

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Bibliographic Details
Published in:Advanced science Vol. 10; no. 3; pp. e2206014 - n/a
Main Authors: Cho, Ik Sung, Gupta, Prerak, Mostafazadeh, Nima, Wong, Sing Wan, Saichellappa, Saiumamaheswari, Lenzini, Stephen, Peng, Zhangli, Shin, Jae‐Won
Format: Journal Article
Language:English
Published: Germany John Wiley & Sons, Inc 01-01-2023
John Wiley and Sons Inc
Wiley
Subjects:
Cell adhesion & migration
Cell division
Cell Encapsulation
Cell Polarity
Hydrogels
Ligands
microenvironments
microfluidics
Oligopeptides
Stem cells
Viscosity
cell encapsulation
hydrogels
cell polarity
microfluidics
microenvironments
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Summary:Various signals in tissue microenvironments are often unevenly distributed around cells. Cellular responses to asymmetric cell‐matrix adhesion in a 3D space remain generally unclear and are to be studied at the single‐cell resolution. Here, the authors developed a droplet‐based microfluidic approach to manufacture a pure population of single cells in a microscale layer of compartmentalized 3D hydrogel matrices with a tunable spatial presentation of ligands at the subcellular level. Cells elongate with an asymmetric presentation of the integrin adhesion ligand Arg‐Gly‐Asp (RGD), while cells expand isotropically with a symmetric presentation of RGD. Membrane tension is higher on the side of single cells interacting with RGD than on the side without RGD. Finite element analysis shows that a non‐uniform isotropic cell volume expansion model is sufficient to recapitulate the experimental results. At a longer timescale, asymmetric ligand presentation commits mesenchymal stem cells to the osteogenic lineage. Cdc42 is an essential mediator of cell polarization and lineage specification in response to asymmetric cell‐matrix adhesion. This study highlights the utility of precisely controlling 3D ligand presentation around single cells to direct cell polarity for regenerative engineering and medicine. A droplet‐based microfluidic approach has been developed to encapsulate single cells at the interface between two distinct compartments in 3D Janus microgels. Using this approach, this study shows that mesenchymal stem cells elongate and polarize when one gel compartment contains a higher concentration of an integrin adhesion ligand than the other, resulting in enhanced osteogenic differentiation independently of gel mechanics.
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ISSN:2198-3844
2198-3844
DOI:10.1002/advs.202206014