Hard sphere-like glass transition in eye lens α-crystallin solutions
Edited by Michael L. Klein, Temple University, Philadelphia, PA, and approved October 14, 2014 (received for review April 16, 2014)
Significance
Normal vision and accommodation rely on the clarity and softness of the eye lens. Hardening of the lens has been linked with presbyopia, the loss of accommodative capability with age, and lens clarity is disrupted in cataract, a leading cause of blindness worldwide. Here, realistically concentrated solutions of a prevalent eye lens structural protein, α-crystallin, which exhibits short-range order needed for lens transparency, are found in addition to show high-concentration dynamical slowing down similar to that of hard-sphere glass transitions. This suggests that analogous investigation of concentrated crystallin mixtures, like those in the living lens, may help to advance understanding of the molecular basis of both presbyopia and cataract.
Abstract
We study the equilibrium liquid structure and dynamics of dilute and concentrated bovine eye lens α-crystallin solutions, using small-angle X-ray scattering, static and dynamic light scattering, viscometry, molecular dynamics simulations, and mode-coupling theory. We find that a polydisperse Percus–Yevick hard-sphere liquid-structure model accurately reproduces both static light scattering data and small-angle X-ray scattering liquid structure data from α-crystallin solutions over an extended range of protein concentrations up to 290 mg/mL or 49% vol fraction and up to ca. 330 mg/mL for static light scattering. The measured dynamic light scattering and viscosity properties are also consistent with those of hard-sphere colloids and show power laws characteristic of an approach toward a glass transition at α-crystallin volume fractions near 58%. Dynamic light scattering at a volume fraction beyond the glass transition indicates formation of an arrested state. We further perform event-driven molecular dynamics simulations of polydisperse hard-sphere systems and use mode-coupling theory to compare the measured dynamic power laws with those of hard-sphere models. The static and dynamic data, simulations, and analysis show that aqueous eye lens α-crystallin solutions exhibit a glass transition at high concentrations that is similar to those found in hard-sphere colloidal systems. The α-crystallin glass transition could have implications for the molecular basis of presbyopia and the kinetics of molecular change during cataractogenesis.
Acknowledgments
The authors are grateful to Lucia Casal-Dujat for her help with the characterization of the glass-like α-crystallin solution. G.F. and N.D. gratefully acknowledge financial support from the Swiss National Science Foundation (Grants PP0022_119006 and PP00P2_140822/1). A.S. and P.S. gratefully acknowledge financial support from the Swiss National Science foundation (Grants 200020-109499, 200020-117755, and 200021-127192), the State Secretariat for Education and Research of Switzerland, and the Marie Curie Network on Dynamical Arrest of Soft Matter and Colloids (Grant MCRTN-CT-2003504712). N.D. acknowledges support from the Swiss National Science Foundation (Project PBELP2-130895). A.S. acknowledges financial support from the Swedish Research Council (Grants 621-2012-2422 and 2009-6794). Research by G.T. reported in this paper was supported by the National Eye Institute of the National Institutes of Health under Award R15EY018249.
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Published online: November 10, 2014
Published in issue: November 25, 2014
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Acknowledgments
The authors are grateful to Lucia Casal-Dujat for her help with the characterization of the glass-like α-crystallin solution. G.F. and N.D. gratefully acknowledge financial support from the Swiss National Science Foundation (Grants PP0022_119006 and PP00P2_140822/1). A.S. and P.S. gratefully acknowledge financial support from the Swiss National Science foundation (Grants 200020-109499, 200020-117755, and 200021-127192), the State Secretariat for Education and Research of Switzerland, and the Marie Curie Network on Dynamical Arrest of Soft Matter and Colloids (Grant MCRTN-CT-2003504712). N.D. acknowledges support from the Swiss National Science Foundation (Project PBELP2-130895). A.S. acknowledges financial support from the Swedish Research Council (Grants 621-2012-2422 and 2009-6794). Research by G.T. reported in this paper was supported by the National Eye Institute of the National Institutes of Health under Award R15EY018249.
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This article is a PNAS Direct Submission.
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The authors declare no conflict of interest.
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Hard sphere-like glass transition in eye lens α-crystallin solutions, Proc. Natl. Acad. Sci. U.S.A.
111 (47) 16748-16753,
https://doi.org/10.1073/pnas.1406990111
(2014).
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