Macromolecular Crowding as an Intracellular Stimulus for Responsive Nanomaterials

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Cellular Biology

Background:

• Stimuli-responsive materials are crucial for biological, materials, and sensing applications.
• Thermoresponsive polymers typically change properties with temperature variations.

Purpose of the Study:

• To introduce biomacromolecule crowding as a novel endogenous stimulus for materials.
• To develop polymers that respond to macromolecule concentration changes in biological environments.

Main Methods:

• Synthesized poly(2-oxazoline) amphiphiles with specific thermoresponsive properties.
• Investigated nanoemulsion stability and fusion in response to temperature and crowding agents.
• Tested nanoemulsion behavior upon injection into living zebrafish embryos.

Main Results:

• Poly(2-oxazoline) amphiphiles stabilized nanoemulsions below their lower critical solution temperature (LCST).
• Nanoemulsion fusion occurred above the LCST or upon addition of crowding agents (polymers, proteins) at physiological temperatures.
• Injected nanoemulsions fused within zebrafish embryo cells, demonstrating cytosol as a stimulus.

Conclusions:

• Thermoresponsive materials can be engineered to be "crowding responsive," reacting to macromolecule concentration.
• Biomacromolecule crowding offers a new stimulus for designing smart materials for biological applications.
• This work expands the potential applications of stimuli-responsive polymers in cellular environments.