Novel protein peptide hydrogels

Abstract

The present invention broadly provides novel peptides that can be used to form hydrogels. The peptides are short (preferably 30 amino acid residues or less) and include hydrophilic and hydrophobic segments joined by a turning segment. The hydrogels are formed by altering the pH of a solution of these peptides to an acidic level, or by introducing a source of ions into a solution of these peptides. The resulting hydrogels are shear thinning gels that have high storage moduli and high rates of recovery after destruction. They find use in medical applications, including tissue engineering.

We claim: 
     
         1 . A method of fowling a gel, said method comprising:
 providing a peptide solution, said solution comprising at least about 0.1% by weight peptide, based upon the total weight of the solution taken as 100% by weight, and said peptide comprising less than about 30 amino acid residues; and   carrying out at least one of the following:
 (a) adjusting the pH of said peptide solution to a level of from about 1 to about 6 so as to form the gel; or 
 (b) introducing a source of ions into said peptide solution so as to form the gel, said ions being selected from the group consisting of ions of Group I and Group II metals. 
   
     
     
         2 . The method of  claim 1 , wherein said ions of Group I and Group II metals are selected from the group consisting of Ca, Na, Mg, K, and Zn ions. 
     
     
         3 . The method of  claim 1 , wherein said peptide comprises less than about 20 amino acid residues. 
     
     
         4 . The method of  claim 1 , where the molar ratio of peptide to ion in (a) is from about 1:5 to about 1:15. 
     
     
         5 . The method of  claim 1 , wherein said peptide solution comprises a peptide suspended, dispersed, or dissolved in water. 
     
     
         6 . The method of  claim 1 , wherein the pH of said peptide solution before (a) or (b) is from about 6 to about 12. 
     
     
         7 . The method of  claim 1 , said peptide comprising a hydrophobic terminal region, a turning region, and a hydrophilic terminal region, said turning region being between said hydrophobic and hydrophilic regions. 
     
     
         8 . The method of  claim 7 , wherein said turning region comprises amino acid residues selected from the group consisting of G, L, I, V, A, S, and T. 
     
     
         9 . The method of  claim 7 , wherein said turning region comprises amino acid residues of X 1 SX 2 X 2  (SEQ ID NO:3), in any order, where:
 X 1  is selected from the group consisting of G, I, and V;   each X 2  is individually selected from the group consisting of G, I, V, A, and L; and   at least one of X 1  or X 2  is G.   
     
     
         10 . The method of  claim 7 , wherein said turning region is selected from the group consisting of G, GG, GGG, GGGG (SEQ ID NO:17), GSXX (SEQ ID NO:18), XGSX (SEQ ID NO:19), XXGS (SEQ ID NO:20), SGXX (SEQ ID NO:21), XSGX (SEQ ID NO:22), XXSG (SEQ ID NO:23), GXSX (SEQ ID NO:24), XGXS (SEQ ID NO:25), SXGX (SEQ ID NO:26), XSXG (SEQ ID NO:27), GXXS (SEQ ID NO:28), SXXG (SEQ ID NO:29), where each X is individually selected from the group consisting of G, I, V, A, and L, and each S could be replaced by T. 
     
     
         11 . The method of  claim 7 , wherein said turning region consists of amino acid residues GSII (SEQ ID NO:30). 
     
     
         12 . The method of  claim 7 , wherein said hydrophobic region comprises amino acid residues selected from the group consisting of F, L, I, V, and A. 
     
     
         13 . The method of  claim 7 , wherein said hydrophobic region comprises, in any order, amino acid residues of FLIVI (SEQ ID NO:4). 
     
     
         14 . The method of  claim 7 , wherein said hydrophobic region consists of, in any order, amino acid residues of FLIVI (SEQ ID NO:4). 
     
     
         15 . The method of  claim 7 , wherein said hydrophilic region comprises amino acid residues selected from the group consisting of G, P, D, V, I, L, and A. 
     
     
         16 . The method of  claim 7 , wherein said hydrophilic region is selected from the group consisting of:
 [GPGXD] n  (SEQ ID NO:15), where n is from 1 to 10, and each X is G. or A;   GPGX 1 DGX 2 X 1 X 1 D (SEQ ID NO:14), in any order, where each X 1  is individually selected from the group consisting of A, G, V, I, and L, and X 2  is selected from the group consisting of P, A, G, V, I, and L; and   GPGXD (SEQ ID NO:16), where X is selected from the group consisting of A, G, V, I, and L.   
     
     
         17 . The method of  claim 1 , wherein said gel has a storage modulus of at least about 500 Pa at 22° C. 
     
     
         18 . The method of  claim 1 , wherein said gel has a % recovery of at least about 60% after 10 minutes. 
     
     
         19 . The method of  claim 1 , wherein said gel is a shear thinning gel. 
     
     
         20 . The method of  claim 1 , wherein said gel has an average cell size of from about 10 μm to about 80 μm. 
     
     
         21 . The method of  claim 1 , wherein said gel comprises peptide nanofibers having an average diameter of from about 3 nm to about 30 nm, and an average length of from about 0.3 μm to about 5 μm.