Spatiotemporal Patterning of Living Cells with Extracellular DNA Programs

Area of Science:

• Synthetic Biology
• Biochemistry
• Cell Biology

Background:

• Current extracellular reaction networks lack feedback and out-of-equilibrium dynamics for spatiotemporal control.
• Engineering extracellular environments to precisely control intracellular composition is challenging.

Purpose of the Study:

• To develop functional enzyme-DNA molecular programs in extracellular media for spatiotemporal control of cellular processes.
• To demonstrate the ability to encode temporal and positional information into living cells using synthetic extracellular programs.

Main Methods:

• Utilized enzyme-DNA molecular programs within an extracellular medium supporting human cell growth.
• Constructed an internalization program to deliver fluorescent DNA into cells, maintaining functionality for at least 48 hours.
• Engineered a spatially inhomogeneous program to generate tunable reaction-diffusion patterns for cell internalization.

Main Results:

• Demonstrated functional enzyme-DNA programs in extracellular media for controlling cell internalization.
• Achieved precise temporal and positional control over cell internalization using nonequilibrium dynamics.
• Generated a tunable two-band pattern of cell internalization via reaction-diffusion dynamics.

Conclusions:

• Synthetic extracellular programs can provide temporal and positional information to living cells, emulating developmental mechanisms.
• Nonequilibrium reactive extracellular media offer potential applications in biomolecular tracking, tissue engineering, and smart bandages.