Size regulation of multiple organelles competing for a limiting subunit pool.

How cells regulate the size of intracellular structures and organelles is a longstanding question. Recent experiments suggest that size control of intracellular structures is achieved through the depletion of a limiting subunit pool in the cytoplasm. While the limiting pool model ensures organelle-to-cell size scaling, it does not provide a mechanism for robust size control of multiple co-existing structures. Here we develop a generalized theory for size-dependent growth of intracellular structures to demonstrate that robust size control of multiple intracellular structures, competing for a limiting subunit pool, is achieved via a negative feedback between the growth rate and the size of the individual structure. This design principle captures size maintenance of a wide variety of subcellular structures, from cytoskeletal filaments to three-dimensional organelles. We identify the feedback motifs for structure size regulation based on known molecular processes, and compare our theory to existing models of size regulation in biological assemblies. Furthermore, we show that positive feedback between structure size and growth rate can lead to bistable size distribution and spontaneous size selection. Author summary: Organelle size control is essential for the proper physiological functioning of eukaryotic cells, but the underlying mechanisms of size regulation remain poorly understood. By developing a general theory for organelle size control, we show that robust size control of intracellular structures and organelles is achieved via a negative feedback between individual organelle size and their net growth rates. This design principle not only describes size maintenance of single organelles, but also ensures size stability of multiple co-existing organelles that are built from a limiting pool of subunits. Our results delineate the role of limiting pool as a size scaling mechanism rather than a size control mechanism, supporting the idea that negative feedback control of organelle size via depletion of a limiting subunit pool is not sufficient to maintain the size of multiple competing organelles. In the case of positive feedback between organelle size and growth rate, our model reproduces phenomena such as bistability in organelle size distribution and spontaneous emergence of cell polarity. [ABSTRACT FROM AUTHOR]