Cataracts: How proteins shape our vision

Our cells are bustling with activity: proteins and other biomolecules are crowded together in a very small space, an effect known as “macromolecular crowding”. This affects the stability, viscosity and reactivity of proteins. These effects are not only exciting from a biophysical perspective, but also have direct medical relevance: diseases involving defective protein deposits, such as Alzheimer's, and lens disorders, such as cataracts and presbyopia, are closely related to this phenomenon.

Eye lens proteins as a model for binary protein systems

Physical models for solutions containing only one protein have already been well researched and are reliable. However, natural fluids such as cell plasma or blood serum consist of complex systems whose dynamics and flow properties are still poorly understood. The researchers have chosen the crystalline proteins of the eye lens as an illustrative model system: α-crystallin behaves like a large, almost inelastic sphere, while γB-crystallin tends to form temporary clusters at low temperatures. 

“The system is simple because it has only two components: relatively spherical proteins – hard spheres without subdomains and internal dynamics. This allows us to approach more complex systems step by step,” sums up Dr. Olaf Holderer from Forschungszentrum Jülich, an instrument scientist at J-NSE.

Simple rules, major impact

The results show that phase behaviour and viscosity at high protein concentrations can be described surprisingly well using simple mixing rules. This works like a kind of average value for the properties of the individual proteins. Deviations only occur in very small quantities or directly at the phase boundary. The interaction of larger groups of proteins also follows these simple mixing rules.

Microscopically oversimplified

On a microscopic scale, neutron spin echo spectroscopy performed at the J-NSE at the MLZ shows that short-lived clusters and directed surface interactions influence the collective motion of proteins.

The general trends are recognised by the mixing rules, but they overestimate the propagation on small length scales. At the microscopic level, the specific protein-protein interactions therefore require more detailed models. 

Outlook for the lens

According to the study, small modifications to the protein connections can have a significant impact on the flexibility and transparency of the eye lens. This provides starting points for new therapeutic strategies for lens diseases.

“The next step is to test the approach with more complex mixtures and to use computer simulations to investigate length scales where our simple approach is no longer sufficient,” says Prof. Anna Stradner, who heads the research group in Lund, Sweden.

Models that take into account directed protein interactions are planned, as well as dynamic simulations of several crystalline proteins to clarify the relationship between the resilience of the lens and movement on the smallest scale.