Berlin 2018 – wissenschaftliches Programm
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CPP: Fachverband Chemische Physik und Polymerphysik
CPP 76: Focus: Polymers in Multi-Component and Aqueous Solutions II - organized by Jens-Uwe Sommer and Debashish Mukherji
CPP 76.1: Topical Talk
Freitag, 16. März 2018, 09:30–10:00, C 130
Optimal inhibition and spatial organization of irreversible protein aggregation using liquid compartments — •Christoph A. Weber1,2, Thomas Michaels1, and L. Mahadevan1 — 1Harvard John A. Paulson School of Engineering and Applied Science, Cambridge — 2Max Planck Institute for the Physics of Complex Systems, Dresden
Protein aggregation in cells is an ubiquitous phenomenon and linked to a large variety of diseases, such as Alzheimer's and Parkinson's disease, amyloidosis or type II diabetes. So far, there is no effective strategy to suppress or inhibit protein aggregation in these systems. Typically, it has been suggested to design drugs which stabilize monomers against aggregation, or block the surface or the ends of aggregates. We show that this treatment strategy can be optimized increasing dramatically the life time of the cell. In addition, we suggest a novel strategy, namely to spatially segregate protein aggregation in distinct liquid-like cellular compartments in a controllable fashion. Many cells actually use droplet-like compartments to spatially organize the cellular cytoplasm but only little is known about their biological function. Here, we show that liquid compartments are ideally suited to spatially organize protein aggregation. Aggregation only occurring in these compartments keeps the toxic aggregates away from the sensible intracellular surrounding and allows subsequent localized and specific degradation by the cellular machinery or drugs. Since the compartment assembly creates costs we employ optimal control theory to determine the optimal physical parameter for spatial segregation of protein aggregation.