Speaker
Description
Biomolecular self-assembly lies at the very heart of the function of living cells, where it organizes individual components into functional biological machines. The macromolecular sub-units typically correspond to proteins, whose shapes have been optimized over millions of years of evolution to ensure a proper functionality of the self-assembled structures. However, in pathological cases, proteins fail to achieve the optimal folding, which often leads to complex ill-fitting shapes. This produces geometrical incompatibility, which leads to frustrated interactions between the sub-units. Surprisingly, despite a huge variability in protein structure, such misfolded units tend to robustly self-assemble into aggregates with well-defined morphologies. Interestingly, these structures display a clear preference for slimmer topologies, such as fiber aggregates. This emergent principle of dimensionality reduction suggests that the aggregation of irregular components derives from the generic physical principles, rather than the microscopic details of the interactions.
Inspired by this idea, we model the frustrated self-assembly of ill-shaped proteins as coarse-grained anisotropic particles, whose interactions depend on their relative orientations and positions in space. This simple model successfully reproduces a hierarchy of aggregate morphologies and gives pointers to the origins of dimensionality reduction.
Keyword-1 | self-assembly |
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Keyword-2 | frustration |
Keyword-3 | statistical models |