Effects of systematic variation of amino acid sequence on the mechanical properties of a self-assembling, oligopeptide biomaterial

Michael Caplan, Elissa M. Schwartzfarb, Shuguang Zhang, Roger D. Kamm, Douglas A. Lauffenburger

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)225-236
Number of pages12
JournalJournal of Biomaterials Science, Polymer Edition
Volume13
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Oligopeptides
Biocompatible Materials
Biomaterials
Amino acids
Amino Acid Sequence
Amino Acids
Mechanical properties
Elastic moduli
Self assembly
Molecules
Hydrophobicity
Hydrophobic and Hydrophilic Interactions
Peptides
Assays
Materials properties
Substitution reactions
Gels
Salts

Keywords

  • Protein engineering
  • Rational design
  • Shear modulus

ASJC Scopus subject areas

  • Biophysics
  • Biomaterials

Cite this

Effects of systematic variation of amino acid sequence on the mechanical properties of a self-assembling, oligopeptide biomaterial. / Caplan, Michael; Schwartzfarb, Elissa M.; Zhang, Shuguang; Kamm, Roger D.; Lauffenburger, Douglas A.

In: Journal of Biomaterials Science, Polymer Edition, Vol. 13, No. 3, 2002, p. 225-236.

Research output: Contribution to journalArticle

Caplan, Michael ; Schwartzfarb, Elissa M. ; Zhang, Shuguang ; Kamm, Roger D. ; Lauffenburger, Douglas A. / Effects of systematic variation of amino acid sequence on the mechanical properties of a self-assembling, oligopeptide biomaterial. In: Journal of Biomaterials Science, Polymer Edition. 2002 ; Vol. 13, No. 3. pp. 225-236.
@article{61accfc0c9c44ace9717bd3acc2c5650,
title = "Effects of systematic variation of amino acid sequence on the mechanical properties of a self-assembling, oligopeptide biomaterial",
abstract = "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.",
keywords = "Protein engineering, Rational design, Shear modulus",
author = "Michael Caplan and Schwartzfarb, {Elissa M.} and Shuguang Zhang and Kamm, {Roger D.} and Lauffenburger, {Douglas A.}",
year = "2002",
doi = "10.1163/156856202320176493",
language = "English (US)",
volume = "13",
pages = "225--236",
journal = "Journal of Biomaterials Science, Polymer Edition",
issn = "0920-5063",
publisher = "Taylor and Francis Ltd.",
number = "3",

}

TY - JOUR

T1 - Effects of systematic variation of amino acid sequence on the mechanical properties of a self-assembling, oligopeptide biomaterial

AU - Caplan, Michael

AU - Schwartzfarb, Elissa M.

AU - Zhang, Shuguang

AU - Kamm, Roger D.

AU - Lauffenburger, Douglas A.

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - Protein engineering

KW - Rational design

KW - Shear modulus

UR - http://www.scopus.com/inward/record.url?scp=1842845084&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1842845084&partnerID=8YFLogxK

U2 - 10.1163/156856202320176493

DO - 10.1163/156856202320176493

M3 - Article

VL - 13

SP - 225

EP - 236

JO - Journal of Biomaterials Science, Polymer Edition

JF - Journal of Biomaterials Science, Polymer Edition

SN - 0920-5063

IS - 3

ER -