16 research outputs found
Achieving Controlled Biomolecule-Biomaterial Conjugation
The conjugation of biomolecules can impart materials with the bioactivity necessary to modulate specific cell behaviors. While the biological roles of particular polypeptide, oligonucleotide, and glycan structures have been extensively reviewed, along with the influence of attachment on material structure and function, the key role played by the conjugation strategy in determining activity is often overlooked. In this review, we focus on the chemistry of biomolecule conjugation and provide a comprehensive overview of the key strategies for achieving controlled biomaterial functionalization. No universal method exists to provide optimal attachment, and here we will discuss both the relative advantages and disadvantages of each technique. In doing so, we highlight the importance of carefully considering the impact and suitability of a particular technique during biomaterial design
Amino Acid Sequence in Constitutionally Isomeric Tetrapeptide Amphiphiles Dictates Architecture of One-Dimensional Nanostructures
The switching of
two adjacent amino acids can lead to differences
in how proteins fold thus affecting their function. This effect has
not been extensively explored in synthetic peptides in the context
of supramolecular self-assembly. Toward this end, we report here the
use of isomeric peptide amphiphiles as molecular building blocks to
create one-dimensional (1D) nanostructures. We show that four peptide
amphiphile isomers, with identical composition but a different sequence
of their four amino acids, can form drastically different types of
1D nanostructures under the same conditions. We found that molecules
with a peptide sequence of alternating hydrophobic and hydrophilic
amino acids such as VEVE and EVEV self-assemble into flat nanostructures
that can be either helical or twisted. On the other hand, nonalternating
isomers such as VVEE and EEVV result in the formation of cylindrical
nanofibers. Furthermore, we also found that when the glutamic acid
is adjacent to the alkyl tail the supramolecular assemblies appear
to be internally flexible compared to those with valine as the first
amino acid. These results clearly demonstrate the significance of
peptide side chain interactions in determining the architectures of
supramolecular assemblies
Research data supporting "Residue-Specific Solvation Directed Thermodynamic and Kinetic Control over Peptide Self-Assembly with 1D/2D Structure Selection"
Experimental research raw data supporting the publication by Lin, Y. et al, 2019, "Residue-Specific Solvation Directed Thermodynamic and Kinetic Control over Peptide Self-Assembly with 1D/2D Structure Selection", ACS Nano. DOI: 10.1021/acsnano.8b08117.
Molecular simulation data is available upon reasonable request from [email protected] research raw data supporting the publication by Lin, Y. et al, 2019, "Residue-Specific Solvation Directed Thermodynamic and Kinetic Control over Peptide Self-Assembly with 1D/2D Structure Selection", ACS Nano. DOI: 10.1021/acsnano.8b08117. Molecular simulation data is available upon reasonable request from [email protected]
Residue-Specific Solvation-Directed Thermodynamic and Kinetic Control over Peptide Self-Assembly with 1D/2D Structure Selection
Understanding the self-organization and structural transformations of molecular ensembles is important to explore the complexity of biological systems. Here, we illustrate the crucial role of cosolvents and solvation effects in thermodynamic and kinetic control over peptide association into ultrathin Janus nanosheets, elongated nanobelts, and amyloid-like fibrils. We gained further insight into the solvation-directed self-assembly (SDSA) by investigating residue-specific peptide solvation using molecular dynamics modeling. We proposed the preferential solvation of the aromatic and alkyl domains on the peptide backbone and protofibril surface, which results in volume exclusion effects and restricts the peptide association between hydrophobic walls. We explored the SDSA phenomenon in a library of cosolvents (protic and aprotic), where less polar cosolvents were found to exert a stronger influence on the energetic balance at play during peptide propagation. By tailoring cosolvent polarity, we were able to achieve precise control of the peptide nanostructures with 1D/2D shape selection. We also illustrated the complexity of the SDSA system with pathway-dependent peptide aggregation, where two self-assembly states (i.e., thermodynamic equilibrium state and kinetically trapped state) from different sample preparation methods were obtained
Residue-Specific Solvation-Directed Thermodynamic and Kinetic Control over Peptide Self-Assembly with 1D/2D Structure Selection
Controlled Sub-Nanometer Epitope Spacing in a Three-Dimensional Self-Assembled Peptide Hydrogel
Murine model for cystic fibrosis bone disease demonstrates osteopenia and sex-related differences in bone formation
As the incidence of cystic fibrosis (CF) bone disease is increasing, we analyzed CF transmembrane conductance regulator (CFTR) deficient mice (CF mice) to gain pathogenic insights. In these studies comparing adult (14 wk) CF and C57BL/6J mice, both bone length and total area were decreased in CF mice. Metaphyseal trabecular and cortical density were also decreased, as well as diaphyseal cortical and total density. Trabecular bone volume was diminished in CF mice. Female CF mice revealed decreased trabecular width and number compared with C57BL/6J, whereas males demonstrated no difference in trabecular number. Female CF mice had reduced mineralizing surface and bone formation rates. Conversely, male CF mice had increased mineralizing surface, mineral apposition, and bone formation rates compared with C57BL/6J males. Bone formation rate was greater in males compared with female CF mice. Smaller bones with decreased density in CF, despite absent differences in osteoblast and osteoclast surfaces, suggest CF transmembrane conductance regulator influences bone cell activity rather than number. Differences in bone formation rate in CF mice are suggestive of inadequate bone formation in females but increased bone formation in males. This proanabolic observation in male CF mice is consistent with other clinical sex differences in CF