Decoding mechanoregulation in immunological synapses using biomimetic artificial cells

Area of Science:

• Biomaterials Science
• Cellular Mechanobiology
• Immunology

Background:

• Mechanical force is crucial for cell-cell interactions (CCIs) and immune cell function.
• Existing biochemical methods lack control over cellular phenotypes, and synthetic systems fail to capture cellular complexity.
• Studying force-dependent CCIs requires advanced models that mimic cellular dynamics.

Purpose of the Study:

• To introduce kpiCells, a novel biomaterial platform for studying mechanical force-driven cell-cell interactions.
• To enable precise control over cellular states and mimic complex subcellular features.
• To investigate mechanosensing and force exertion in T cell systems.

Main Methods:

• Developed kpiCells, a biomaterial platform with biomimetic membrane-endoplasmic architecture.
• Utilized modular mechanical, chemical, and topographical inputs for cellular state phenocopying.
• Applied kpiCells to T cell systems for integrated pathway interrogation and force measurement.

Main Results:

• kpiCells successfully engage in physiological CCIs and replicate subcellular features.
• Demonstrated integrated interrogation of afferent mechanosensing and efferent force-exertion pathways in T cells.
• Enabled measurement of piconewton-scale forces at individual T cell antigen receptors and cell-cell force fingerprints.

Conclusions:

• kpiCells serve as a bionic model for studying mechanical force in cell-cell interactions.
• The platform offers unprecedented control and mimicry of living cell systems.
• Establishes a new paradigm for synthetic material design approaching the complexity of living cells.