title: D-amino acids modulate the cellular response of enzymatic-instructed supramolecular nanofibers of small peptides.
abstract: Peptides made of D-amino acids, as the enantiomer of corresponding L-peptides, are able to resist proteolysis. It is, however, unclear or much less explored whether or how D-amino acids affect the cellular response of supramolecular nanofibers formed by enzyme-triggered self-assembly of D-peptides. In this work, we choose a cell compatible molecule, Nap-L-Phe-L-Phe-L-(p)Tyr (LLL-1P), and systematically replace the L-amino acids in this tripeptidic precursor or its hydrogelator by the corresponding D-amino acid(s). The replacement of even one D-amino acid in this tripeptidic precursor increases its proteolytic resistance. The results of static light scattering and TEM images show the formation of nanostructures upon the addition of alkaline phosphatase, even at concentrations below the minimum gelation concentration (mgc). All these isomers are able to form ordered nanostructures and exhibit different morphologies. According to the cell viability assay on these stereochemical isomers, cells exhibit drastically different responses to the enantiomeric precursors, but almost same responses to the enantiomeric hydrogelators. Furthermore, the different cellular responses of LLL-1P and DDD-1P largely originate from the ecto-phosphatases catalyzed self-assembly of DDD-1 on the surface of cells. Therefore, this report not only illustrates a new way for tailoring the properties of supramolecular assemblies, but also provides new insights to answering the fundamental question of how mammalian cells respond to enzymatic formation of nanoscale supramolecular assemblies (e.g., nanofibers) of D-peptides.
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, MS 015, Waltham, Massachusetts 02453, United States.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Shi
authors.forename: Xuewen
authors.initials: X
authors.lastname: Du
authors.forename: Dan
authors.initials: D
authors.lastname: Yuan
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.forename: Yibing
authors.initials: Y
authors.lastname: Huang
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D057139:Nanofibers / Q000008:administration & dosage*; D049329:Nanostructures / Q000008:administration & dosage; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects
chemical_list: D000596:Amino Acids; D020100:Hydrogels; D010455:Peptides