Self-assembly of peptide-amphiphile nanofibers under physiological conditions
The present invention provides a method of promoting neuron growth and development by contacting cells with a peptide amphiphile molecule in an aqueous solution in the presence of a metal ion. According to the method, the peptide amphiphile forms a cylindrical micellar nanofiber composed of beta-sheets, which promote neuron growth and development.
1. A method of promoting neuron growth and development comprising
(a) contacting neurons undergoing neuron growth and development with a peptide amphiphile molecule in an aqueous solution, wherein said peptide amphiphile molecule comprises a single C 6 to C 22 linear hydrocarbon segment covalently linked to a peptide segment comprising the bioactive epitope sequence IKVAV (SEQ ID NO:1), and
(b) contacting said peptide amphiphile molecule with an effective amount of a metal ion selected from Ca 2+, Mg 2+, , Fe 2+, , Zn 2+, , and Fe 3+ , and combinations thereof sufficient to induce formation of a cylindrical micellar nanofiber composed of beta-sheets, wherein said nanofibers promote the neuron growth and development.
2. The method of claim 1 , wherein said contacting step occurs under physiological conditions.
3. The method of claim 1 , wherein said metal ion is present in a bodily fluid.
4. The method of claim 1 , wherein said peptide amphiphile molecule has a net charge at substantially physiological pH.
5. The method of claim 1 , wherein said hydrocarbon segment is linked to the N-terminus of said peptide segment.
6. The method of claim 1 , wherein said cylindrical micellar nanofiber has a conical shape comprised of a narrow hydrocarbon tail at one end and a bulkier peptide region at the other.
7. The method of claim 1 , wherein said cylindrical micellar nanofiber displays a secondary structure that includes both beta-sheets and alpha-helices.
8. The method of claim 1 , wherein said contacting said neurons undergoing neuron growth and development with said peptide amphiphile administering comprises parenteral administration of an aqueous solution comprising said peptide amphiphile.
9. The method of claim 1 , wherein said neurons undergoing neuron growth and development are further contacted with a therapeutic agent selected from the group consisting of growth factors, co-factors, and activators.
10. A method of promoting neuron growth and development comprising
(a) contacting neurons undergoing neuron growth and development with a peptide amphiphile molecule in an aqueous solution, wherein said peptide amphiphile molecule comprises a single C 6 to C 22 linear hydrocarbon segment covalently linked to a peptide segment comprising the bioactive epitope sequence IKVAV (SEQ ID NO:1), and
(b) contacting said peptide amphiphile molecule with an effective amount of a Ca 2+ sufficient to induce formation of a cylindrical micellar nanofiber composed of beta-sheets, wherein said nanofibers promote the neuron growth and development.