Strength limit of entropic elasticity in beta-sheet protein domains

Elasticity and strength of proteins influence their biological functions. Under external forces, many proteins exhibit entropic elasticity with a characteristic stiffening elastic behavior and unravel due to the rupture of interstrand H-bonds. We develop a fracture mechanics based theoretical framework that considers the free energy competition between entropic elasticity of polypeptide chains and rupture of peptide hydrogen bonds, which we use here to provide an explanation for the intrinsic strength limit of protein domains at vanishing rates [1, 2]. Our analysis predicts that individual protein domains stabilized only by hydrogen bonds cannot exhibit rupture forces larger than 100–300 pN in the asymptotic quasi-static limit. This result explains earlier experimental and computational observations that suggest such a universal, asymptotic strength limit at vanishing pulling rates. We show that the rupture strength of H-bond assemblies in beta-sheets is governed by geometric confinement effects, suggesting that clusters of at most 3–4 H-bonds break concurrently, even under uniform shear loading of a much larger number of H-bonds. These strength, elasticity and size effect predictions all agree well with recent experimental findings and proteomics data. Our model confirms that fracture mechanics concepts, previously primarily applied to macroscale fracture phenomena, can also be directly applied at nanoscale, to be used for describing failure mechanisms in protein materials. Our strength and optimal size predictions lead to a key hypothesis: confined H-bond clusters are prevalent in alpha helices, beta-sheets and beta-solenoids, perhaps as an evolutionary design principle that derives from generic mechanical properties of the fundamental building blocks of life.

Download Full-text

Asymptotic Strength Limit of Hydrogen Bond Assemblies in Proteins at Vanishing Pulling Rates

MRS Proceedings ◽

10.1557/proc-1062-nn05-08 ◽

2007 ◽

Vol 1062 ◽

Author(s):

Sinan Keten ◽

Markus J. Buehler

Keyword(s):

Hydrogen Bond ◽

Hydrogen Bonds ◽

Computational Studies ◽

Entropic Elasticity ◽

Strength Limit ◽

Wide Range ◽

Peptide Hydrogen ◽

Polypeptide Chains ◽

Limiting Value ◽

Intrinsic Strength

ABSTRACTExperimental and computational studies on mechanical unfolding of proteins suggest that rupture forces approach a limiting value of a few hundred pN at vanishing pulling velocities. We develop a fracture mechanics based theoretical framework that considers the free energy competition between entropic elasticity of polypeptide chains and rupture of peptide hydrogen bonds, which we use here to provide an explanation for the intrinsic strength limit of proteins. Our analysis predicts that individual protein domains stabilized by hydrogen bonds can not exhibit rupture forces larger than approximately ≈200 pN, regardless of the presence of a large number of hydrogen bonds. This result explains a wide range of experimental and computational observations.

Download Full-text