title: Importance of crowding in signaling, genetic, and metabolic networks.
abstract: It is now well established that the cell is a highly crowded environment. Yet, the effects of crowding on the dynamics of signaling pathways, gene regulation networks, and metabolic networks are still largely unknown. Crowding can alter both molecular diffusion and the equilibria of biomolecular reactions. In this chapter, we first discuss how diffusion can affect biochemical networks. Diffusion of transcription factors can increase noise in gene expression, while diffusion of proteins between intracellular compartments or between cells can reduce concentration fluctuations. In push-pull networks diffusion can impede information transmission, while in multisite protein modification networks diffusion can qualitatively change the macroscopic response of the system, such as the loss or emergence of bistability. Moreover, diffusion can directly change the metabolic flux. We describe how crowding affects diffusion, and thus how all these phenomena are influenced by crowding. Yet, a potentially more important effect of crowding on biochemical networks is mediated via the shift in the equilibria of bimolecular reactions, and we provide computational evidence that supports this idea. Finally, we discuss how the effects of crowding can be incorporated in models of biochemical networks.
authors.affiliation: FOM Institute AMOLF, Amsterdam, The Netherlands. Electronic address: tenwolde@amolf.nl.
authors.forename: Pieter Rein
authors.initials: PR
authors.lastname: ten Wolde
authors.affiliation: FOM Institute AMOLF, Amsterdam, The Netherlands.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mugler
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002467:Cell Nucleus / Q000502:physiology*; D006801:Humans; D055442:Metabolome / Q000502:physiology*; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors
keywords: Biochemical reactions; Cellular information transmission; Crowding in cell; Gene regulation; Membrane rebinding; Protein modification