Rapidly rendering cells phagocytic through a cell surface display technique and concurrent Rac activation

Area of Science:

• Cell Biology
• Molecular Biology
• Biotechnology

Background:

• Cell surface signaling regulates critical cellular functions like migration and phagocytosis.
• Understanding the minimal molecular requirements for phagocytosis is crucial for harnessing cellular functions.
• Existing techniques lack the speed to rapidly reconfigure cell surface properties.

Purpose of the Study:

• To develop a technique for inducible cell surface presentation of molecules.
• To identify the minimal molecular players sufficient for inducing phagocytosis.
• To engineer phagocytic cells for potential therapeutic applications.

Main Methods:

• Developed a technique for inducible, rapid (minutes) cell surface display of molecules.
• Simultaneously induced cell surface display of the MFG-E8 C2 domain and activated Rac.
• Used HeLa cells engineered to bind and engulf apoptotic Jurkat cells.

Main Results:

• Engineered HeLa cells exhibited phagocytic activity, binding and engulfing apoptotic Jurkat cells.
• Inducible cell surface display of the MFG-E8 C2 domain and Rac activation were both necessary for phagocytosis.
• The combination of target cell attachment and actin reorganization constitutes minimal phagocytosis triggers.

Conclusions:

• The developed technique allows rapid, inducible control over cell surface properties.
• Phagocytosis minimally requires both target cell recognition (via MFG-E8 C2 domain) and actin reorganization (via Rac activation).
• This approach holds promise for targeted cell-based therapies to eliminate unwanted cells.