Cellular Compartmentalization as a Physical Regulation of Biological Processes
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Cells compartmentalize biochemical processes taking advantage of physical barriers in the form of membranes. Eukaryotes have a wide diversity of membrane-based compartments that can be used in this context, with the main ones being the extracellular membrane, which separates the inside from the outside of the cell, and the nuclear membrane, that separates the nucleus from the cytoplasm. The nuclear membrane not only isolates and protects the DNA and the transcription and replication processes from the other processes that are taking place in the cytoplasm, but also has an active role in the regulation of cellular signaling. The TGF-ß pathway is one of the most important and conserved signaling cascades, and it takes advantage of compartmentalization using a well-tuned balance between import and export rates of active and inactive forms of key proteins. Thus, compartmentalization serves as an additional regulatory mechanism, physically isolating transcription factors from their targets, influencing the dynamics and strength of signal transduction. his contribution focuses on this biophysical layer of regulation. It begins with an in-depth review of the TGF-ß pathway and the main regulatory processes underlying this compartmentalization mechanism. Next, we focus on several contributions that study how this compartmentalization shapes the dynamics and ultimately the cell response, and how this separation can be used as readout of several cellular responses. Finally, we introduce a simplified mathematical approach to study this process derived using a generalized formulation.