Martin Lenz How do proteins manage their frustration?

Self-assembly organizes proteins inside cells.

Proteins in our cells constantly self-assemble to form functional structures. They can create the molecular machines responsible for the production of new proteins, viral capsids and the components of the cell's skeleton, whose structures have been optimized over millions of years of evolution. In some diseases, such as Alzheimer's, proteins with complex non-optimized shapes also self-assemble. Surprisingly, given their disparate shapes and interactions, they form relatively well-defined structures: fibers. Martin Lenz will study the molecular mechanisms underlying this phenomenon, which he calls "dimensional reduction".

Understanding the origin of frustration in protein assembly

If the self-assembly of a set of objects (molecules or small particles) that attract each other but do not fit together perfectly is observed, the resulting aggregates contain misaligned or distorted components. As they are assembled, the initially small misalignments between the first objects accumulate. Newly arrived objects encounter a more constrained environment than their predecessors. During the self-assembly process, geometric frustration accumulates and further assembly is impeded. Preliminary work by Dr. Lenz's team suggests that the aggregates form fibers, "dimensional reduction", to escape frustration. New theoretical and experimental tools must be developed to understand the role of frustration in the self-assembly of complex irregularly shaped objects, including proteins.

Discovering new principles underlying fiber formation in certain diseases

Impulscience supports Dr. Lenz and his team’s work to prove that dimensional reduction is a general principle of self-assembly. To do that, they will develop new theoretical methods on the properties of complex particle assemblies. They will use high-resolution 3D printing and X-ray scattering to probe the self-assembly of colloids (microscopic particles suspended in a liquid) and proteins, allowing them to discover the formation mechanisms. Their work will reveal new principles of how matter is organized. It is a fundamental step forward in the understanding of protein-like objects that will lead to a better understanding of biology and certain diseases. It could also have an impact on engineering objects at the nanometric and microscopic scale, contribute to better control of the manufacturing processes of certain drugs and optimize protein crystallography methods.