Deterministic Single Cell Encapsulation in Asymmetric Microenvironments to Direct Cell Polarity.
Ik Sung Cho1,2, Prerak Gupta1,2, Nima Mostafazadeh2
1Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago College of Medicine, Chicago, IL, 60612, USA.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|December 1, 2022
Summary
Single cells respond to asymmetric ligand presentation by elongating and polarizing. This controlled cell adhesion directs stem cell differentiation for regenerative medicine applications.
Area of Science:
- Biomaterials Science
- Cell Biology
- Regenerative Medicine
Background:
- Cellular responses to microenvironmental signals are crucial but poorly understood, especially in 3D.
- Asymmetric cell-matrix adhesion in 3D environments significantly impacts cell behavior.
Purpose of the Study:
- To investigate single-cell responses to precisely controlled, asymmetric 3D ligand presentation.
- To elucidate the mechanisms of cell polarization and lineage specification driven by cell-matrix interactions.
Main Methods:
- Developed a droplet-based microfluidic system for creating 3D hydrogel microenvironments.
- Engineered tunable, subcellular-level spatial presentation of integrin ligands (Arg-Gly-Asp).
- Utilized single-cell imaging and finite element analysis to quantify cellular responses.
Main Results:
- Cells elongated with asymmetric Arg-Gly-Asp (RGD) ligand presentation and expanded isotropically with symmetric RGD.
- Asymmetric ligand presentation increased membrane tension on the RGD-interacting side.
- Mesenchymal stem cells committed to osteogenic lineage under asymmetric ligand conditions, mediated by Cdc42.
Conclusions:
- Precise control of 3D ligand presentation directs single-cell polarity and behavior.
- Asymmetric cell-matrix adhesion is a key regulator of cell fate decisions.
- This approach offers potential for regenerative engineering and therapeutic development.
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