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Wandering the cellular maze

Abstract: The endoplasmic reticulum (ER) is the largest organelle in eukaryotic cells and consists of a dynamic network of lipid membrane tubules and stacked sheets. This complex network stretches from the nucleus to the cell periphery, serving an essential role in the distribution of lipids, ions and proteins throughout the cell. Defects with ER structure are associated with a variety of human diseases, such as Alzheimer’s and herditary spastic paraplegias, so it is important to understand how the ER network morphology impacts its function–in this talk, we focus specifically on transport. To that end, we combine our novel approach for fast agent-based simulations of particles diffusing on tubular networks with in vivo data on the spreading of photoactivated proteins, in order to quantify how local ER network structure determines protein spreading. We demonstrate that network structure and local connectivity serve to explain some but not all of the observed behavior of proteins in the ER. Network dynamics, such as tubule growth and rearrangement are also implicated, so we additionally develop a dynamic model of the ER that captures its unique, constantly evolving structure. Pairing theoretical modeling with live-cell imaging, we highlight the role the ER network structure plays in protein transport and gain fresh insights into the nature of the network itself.

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