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bioRxiv · 10.1101/2023.03.07.531587

Elastin Recoil is Driven by the Hydrophobic Effect

Jamhawi, N. M.·Koder, R. L.·Wittebort, R. J.
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Abstract

Elastin is an extracellular matrix material found in all vertebrates. Its reversible elasticity, robustness and low stiffness are essential for the function of arteries, lungs, and skin. It is among the most resilient elastic materials known: During a human lifetime, arterial elastin undergoes in excess of 2x109 stretching/contracting cycles without replacement and slow oxidative hardening has been identified as a limiting factor on human lifespan. For over fifty years, the mechanism of entropic recoil has been controversial. Herein, we report a combined NMR and thermomechanical study that establishes the hydrophobic effect as the primary driver of elastin function. Water ordering at the solvent:protein interface was observed as a function of stretch using double quantum 2H NMR and the most extensive thermodynamic analysis performed to date was obtained by measuring elastin length and volume as a function of force and temperature in normal water, heavy water and with co-solvents. When stretched, elastins heat capacity increases, water is ordered proportional to the degree of stretching, the internal energy decreases, and heat is released in excess of the work performed. These properties show that recoil in elastin under physiological conditions is primarily driven by the hydrophobic effect rather than by configurational entropy as is the case for rubber. Consistent with this conclusion are decreases in the thermodynamic signatures when co-solvents that alter the hydrophobic effect are introduced. We propose that hydrophobic effect-driven recoil, as opposed to a configurational entropy mechanism, where hardening from crystallization can occur, is the origin of elastins unusual resilience. SignificanceElastin, found in tissues that require reversible elasticity, has low stiffness and great resiliency. It is a self-assembled material that has been a target for regenerative medicine. However, the basis for its elasticity has been controversial for more than 50 years. Formed from a hydrophobic protein with an equivalent mass of water, the controversy is whether recoil is driven by entropy gain of the protein and/or the water. We demonstrate that matrix water is progressively ordered upon stretching and that the thermodynamics of elastin recoil are those of the hydrophobic effect and different from those of rubber. We conclude that recoil is primarily driven by the hydrophobic effect and suggest that this accounts for elastins low stiffness and high resilience.

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Jamhawi, N. M., Koder, R. L., Wittebort, R. J.. 2023-03-08. Elastin Recoil is Driven by the Hydrophobic Effect. https://doi.org/10.1101/2023.03.07.531587

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