Mesoscale Simulation of Sheet-to-Tubule Transformation in the Endoplasmic Reticulum by Curvature-Promoting Proteins

EmadGhazizadeh

University of Alberta/Department of mechanical engineering

"Mesoscale Simulation of Sheet-to-Tubule Transformation in the Endoplasmic Reticulum by Curvature-Promoting Proteins"

The endoplasmic reticulum (ER) is a highly dynamic organelle that undergoes contin- uous remodeling between tubular and sheet-like structures, driven by the Rtn and Reep protein families. Understanding the physical principles underlying these transitions is cru- cial for elucidating the ER’s role in cellular homeostasis and disease. In this study, we em- ploy mesoscale simulations to investigate the mechanisms by which curvature-promoting proteins regulate ER morphology. Specifically, we explore the influence of protein in- trinsic curvature, protein concentration, and protein sti!ening on tubulation dynamics. Our results indicate that increasing the intrinsic curvature of proteins lowers the pro- tein coverage threshold required for tubulation, while enhanced membrane sti!ness facil- itates curvature propagation at lower protein coverage. A phase diagram is constructed to map the conditions necessary for membrane remodeling, identifying critical curvature and protein coverage thresholds that drive ER transformation. These findings establish a quantitative framework for ER shape regulation, shedding light on the interplay between protein-membrane interactions and mechanical properties in ER morphogenesis. By inte- grating computational predictions, this study advances our understanding of ER structural dynamics and its implications for cellular function.
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