A New Protein Screening and Analysis Tool

Scientists at Argonne National Laboratory have developed a new, unique material – a protein scaffold/biomimetic membrane material – that is an extremely powerful tool for encapsulating and studying the native behavior and structure of membrane and soluble proteins – many, for the first time.

The Membrane Material

The membrane material is a complex fluid with the following properties:

• It is a mixture of a lipid, a polymer amphiphile, a co-surfactant and water.
• It undergoes thermoreversible phase changes: a liquid below a certain temperature, a liquid-crystalline gel above that temperature.
• In the liquid state delicated proteins, enzymes and other biomolecules may be mixed and then ordered by simply raising the temperature above room temperature.
• Magnetic fields may be used to further enhance the orientation of the materials and the encapsulated biomolecules.
• When applied to selected substrate materials, domains can be preferentially oriented.

Laboratory Results

Using the membrane, Argonne researchers have made two interesting discoveries:

• Certain non-ionic, amphiphilic triblock copolymers of PEO-PPO-PEO can be employed as an alternative to more costly and architecturally limited PEG – lipid conjugates for producing biomimetic nanostructures.
• To achieve a strongly anchored triblock copolymer, the PPO chain length must approximate the dimensions of the acyl chain region of the lipid bilayer.

Potential Membrane Uses

• As biomimetic nanostructures to used by medical researchers to study soft tissue cellular wounds: burns, frostbite, radiation exposure, pressure trauma, electric shop, scrapes and abrasions, heart attack and stroke.
• As a drug screening and development tool:
  • for approaches to augment healing of cellular wounds – nano-bandaids,
  • to develop methods for site directed delivery of healing agents - nanocapsules, and
  • to determine ideal polymers for healing soft tissue damage (seal permeablized cell membranes).
• As treatment for nerve regeneration, for example, in spinal cord injuries

Patent

U.S. Patent # 6,537,575, issued March 25, 2003.

Collaboration

Argonne's studies, to date, underscore the complexity of multicomponent self-assembled materials and represent a step toward a fuller understanding of them; however the studies are focused at the molecular scale. To prove the efficacy of these discoveries for health applications, for example, much more research needs to take place at the cell and membrane scales too. Researchers would welcome the opportunity to discuss collaboration possibilities that could lead to further development of the membrane material for use in drug discovery, delivery and tissue engineering applications.

Technical Contact: Millie Firestone, at (630) 252-8298 or firestone@anl.gov .

Licensing Contact: Terry Maynard, at (630) 252-9771 or tmaynard@anl.gov.

Selected Publications

Hay, D. N. T.; Rickert, P. G.; Seifert, S.; Firestone, M. A "Thermoresponsive Nanostructures by Self-Assembly of a Poly(N-isopropylacrylamide)-Lipid Conjugate," accepted to J. Am. Chem. Soc.

Firestone, M.A.; Wolf, A. C.; Seifert, S. "Small-Angle X-ray Scattering Study of the Interaction of Poly(ethylene oxide)-b-Poly(propylene oxide)-b-Poly(ethylene oxide) Triblock Copolymers with Lipid Bilayers," Biomacromolecules (2003), 4(6), 1539-1549.

Firestone, M. A.; Tiede, D.; Seifert, S. Magnetic field-induced ordering of a polymer-grafted biomembrane mimetic hydrogel. J. Phys. Chem. B, 104(11), 2433-2438 (2000).

Firestone, M. A.; Tiede, D. M.; Seifert, S.; Thiyagarajan, P. Stimuli-Responsive Polymer-Grafted Lipid-Based Complex Fluids as Organized Media for Supramolecular Photochemistry. Division of Fuel Chemistry Symposia Preprints, 45(2), 375-379 (2000).

Firestone, M. A.; Tiede, D. M.; Thiyagarajan, P. "Evaluation of Supramolecular Architecture in a Membrane-Mimetic Smart Gel by Neutron and X-ray Scattering", in Proceedings of the Materials Research Using Cold Neutrons at Pulsed Neutron Sources Conference, World Scientific Publ. 160-172 (1999).

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