Effects of systematic variation of amino acid sequence on the mechanical properties of a self-assembling, oligopeptide biomaterial.
In order to elucidate design principles for biocompatible materials that can be created by in situ transformation from self-assembling oligopeptides, we investigate a class of oligopeptides that can self-assemble in salt solutions to form three-dimensional matrices. This class of peptides possesses a repeated sequence of amino acid residues with the type: hydrophobic/negatively-charged/hydrophobic/positively-charged. We systematically vary three chief aspects of this sequence type: (1) the hydrophobic side chains; (2) the charged side chains; and (3) the number of repeats. Each of these has been previously shown to influence the self-assembly properties of these materials. Employing a rheometric assay we measure the shear modulus of gels created from variants of each of these aspects. First, we observe order-of-magnitude changes in shear moduli when we vary oligopeptide length, with biphasic dependence on length. This result may be due to competition between, in short oligopeptides, additional repeats either increasing the diameter of the filaments or increasing the area of interaction between individual molecules and, in large oligopeptides, additional repeats allowing the oligopeptides to fold back upon themselves and decrease their effective length. Second, no statistically significant difference is observed among the hydrophobic variants, suggesting that hydrophobicity and steric overlap are unlikely to play a significant role in filament mechanical properties. Finally, in variation of the charged side chains we observe a small difference in the shear moduli that, if significant, may mean that decreasing the energetic penalty for dehydrating the charged side chains can lead to a stiffer matrix. Overall, we demonstrate that it is possible to achieve order-of-magnitude changes in shear modulus by simple variations of oligopeptide length, while the residue substitutions affect only self-assembly properties. Thus, diverse aspects of these molecules can be designed rationally to yield desirable materials properties of different types.
Caplan
Michael R
MR
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139, USA.
Schwartzfarb
Elissa M
EM
Zhang
Shuguang
S
Kamm
Roger D
RD
Lauffenburger
Douglas A
DA
D000595:Amino Acid Sequence; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry; D001696:Biomechanical Phenomena; D019281:Dimerization; D057927:Hydrophobic and Hydrophilic Interactions; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D017433:Protein Structure, Secondary; D012996:Solutions; D055672:Static Electricity; D013329:Structure-Activity Relationship
D001672:Biocompatible Materials; D009842:Oligopeptides; D012996:Solutions