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Molecular structure of RADA16-I designer self-assembling peptide nanofibers.

ABSTRACT: The designer self-assembling peptide RADA16-I forms nanofiber matrices which have shown great promise for regenerative medicine and three-dimensional cell culture. The RADA16-I amino acid sequence has a ?-strand-promoting alternating hydrophobic/charged motif, but arrangement of ?-strands into the nanofiber structure has not been previously determined. Here we present a structural model of RADA16-I nanofibers, based on solid-state NMR measurements on samples with different schemes for (13)C isotopic labeling. NMR peak positions and line widths indicate an ordered structure composed of ?-strands. The NMR data show that the nanofibers are composed of two stacked ?-sheets stabilized by a hydrophobic core formed by alanine side chains, consistent with previous proposals. However, the previously proposed antiparallel ?-sheet structure is ruled out by measured (13)C-(13)C dipolar couplings. Instead, neighboring ?-strands within ?-sheets are parallel, with a registry shift that allows cross-strand staggering of oppositely charged arginine and aspartate side chains. The resulting structural model is compared to nanofiber dimensions observed via images taken by transmission electron microscopy and atomic force microscopy. Multiple NMR peaks for each alanine side chain were observed and could be attributed to multiple configurations of side chain packing within a single scheme for intermolecular packing.

SUBMITTER: Cormier AR

PROVIDER: S-EPMC3946435 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Molecular structure of RADA16-I designer self-assembling peptide nanofibers.

Cormier Ashley R AR Pang Xiaodong X Zimmerman Maxwell I MI Zhou Huan-Xiang HX Paravastu Anant K AK

ACS nano 20130905 9

The designer self-assembling peptide RADA16-I forms nanofiber matrices which have shown great promise for regenerative medicine and three-dimensional cell culture. The RADA16-I amino acid sequence has a β-strand-promoting alternating hydrophobic/charged motif, but arrangement of β-strands into the nanofiber structure has not been previously determined. Here we present a structural model of RADA16-I nanofibers, based on solid-state NMR measurements on samples with different schemes for (13)C isot ...[more]

PMID: 23977885

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Project description:Multidomain peptides (MDPs) are a class of self-assembling peptides that are organized in a β-sheet motif, resulting in a nanofibrous architecture. This structure is stabilized by hydrophobic packing in the fiber core and a hydrogen-bonding network down the fiber long axis. Under easily controllable conditions, regulated by electrostatic interactions between the peptides and the pH and salt composition of the solvent, the nanofiber length can be dramatically extended, resulting in fiber entanglement and hydrogel formation. One of the chief strengths of this supramolecular material is that the design criteria governing its structure and assembly are robust and permit a wide range of modifications without disruption. This allows the MDPs to be tailored to suit a wide range of applications, particularly in biomedical engineering. For example, delivery of small molecules, proteins, and cells is easily achievable. These materials can be trapped within the matrices of the hydrogel or trapped within the hydrophobic core of the nanofiber, depending on the cargo and the design of the MDP. Interactions between the nanofibers and their cargo can be tailored to alter the release profile, and in the most sophisticated cases, different cargos can be released in a cascading time-dependent fashion. The MDP hydrogel and its cargo can be targeted to specific locations, as the thixotropic nature of the hydrogel allows it to be easily aspirated into a syringe and then delivered from a narrow-bore needle. The sequence of amino acids making up the MDP can also be modified to permit cross-linking or enzymatic degradation. Selection of sequences with or without these modifications allows one to control the rate of degradation in vivo from as rapidly as 1 week to well over 6 weeks as the MDP nanofibers are degraded to their amino acid components. MDP sequences can also be modified to add biomimetic sequences derived from growth factors and other signaling proteins. These chemical signals are displayed at a very high density on the fibers' surface, where they contribute to the modification of cellular behavior. We have used this approach to drive blood vessel formation, which is critical for tissue regeneration generally and more specifically for the treatment of diseases related to poor blood flow. MDPs represent an ideal case of bottom-up design where control of chemical structure leads to control of self-assembly and nanostructure and thereby control of material properties that collectively can control biological function.

Dataset Information

Molecular structure of RADA16-I designer self-assembling peptide nanofibers.

Publications

Molecular structure of RADA16-I designer self-assembling peptide nanofibers.

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