Cytoplasmic Diffusion Case Study

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5. Approaches to model cytoplasmic compartmentalization Cytoplasmic viscosity and hinderance to free diffusion has been modelled in three different ways:
5.1 Concentrated Macromolecular solution
Early models assumed the cytosol to be an unstructured dense bag of macromolecules. In these cases, the tracer can essentially diffuse only within the space present between the macromolecules. The DCR (Diffusion Coefficient Ratio, η/ηο) for a tracer particle in a crowded solution will decrease with the tracer radius and will level off at the inverse of relative bulk viscosity (Graph I, Macromolecule Solution) (Luby-Phelps et al., 1988a). Graph I Relative diffusion coefficient vs tracer size for a monodisperse
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They noted that bacterial cytoplasm is crowded, poly-disperse and in the absence of known motors, diffusion-reliant for metabolic activities. Yet, how metabolism affects the cytoplasm remained untested. Their results suggest that the cytoplasm appears like a simple viscous fluid to particles below a certain size scale (< 30nm), and like a glass-forming liquid to particles above this size. The glass-like properties include caging, dynamic heterogeneity and non-ergodicity. Under natural conditions, this behaviour might reduce diffusion of large macromolecules & hinder cellular activities, yet it does not. Searching for an explanation, they found that metabolic activity suppresses this glassy behaviour by fluidizing the cytoplasm (Figure 6).
Implication of this finding suggests that the surrounding environmental conditions can dramatically alter cytoplasmic properties. They note that the glassy behaviour is exhibited much more in bacterial cytoplasm than in eukaryotic cytoplasm, owing to it being more crowded. In conclusion, their study hints that “metabolism-induced fluidization may help the cell to achieve the delicate balance of attaining extremely high concentrations of biomolecules (to increase metabolism and cell proliferation) without severely compromising macromolecular motion” (Parry

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