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Intracellular spatial organisation : The effects of non-ideal solutions

Abstract : In the cytoplasm of a biological cell there are a myriad of different proteins, lipids and enzymes, each of them performing different tasks. The spatial organisation of these chemical species is crucial for the correct functioning of a cell.In the first part of this thesis we will explore, from a theoretical perspective, two processes where the intracellular medium is patterned and organised, whose common feature is the fact that they both stem from the collective behaviour of a large number of molecules. First, we develop a model for protein aggregation which studies the effect of intracellular obstacles on the coagulation kinetics. Our predictions are then successfully compared with experimental data obtained by our collaborators.The other example refers to the compaction and location of the bacterial chromosome. We suggest that the chromosome segregates from the rest of the cytoplasm, because of steric interactions between DNA and the intracellular crowders, by means of a mechanism reminiscent of liquid-liquid phase separation. Moreover, our study indicates that spatial localisation of the chromosome within the cell is dictated by out-of-equilibrium transcription of mRNAs (which are part of the crowding effect). Our model successfully reproduces the localisation pattern of the Escherichia coli chromosome, which is positioned at the center of the cell before the division of the chromosome and at 1/4 and 3/4 of the cell after division.Building on these examples, in the second part of the thesis we construct a thermodynamically consistent framework to mathematically describe chemical-reaction networks in non-ideal solutions. This framework allows us to generalize the results from the classical theory of ideal networks, and aids in elucidating the connection between out-of-equilibrium chemical reactions and phase separation for a large class of networks, known as complex-balanced networks. Complex-balanced networks are is a class of chemical reaction networks that is less restrictive than detailed-balanced ones. Given that complex balancing can be fully determined from the topology of the network, we discuss how this topological property of the network can constrain the dynamics of the solution, and what behaviour one can expect when complex balancing is broken.
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Submitted on : Tuesday, January 11, 2022 - 4:49:22 PM
Last modification on : Tuesday, June 28, 2022 - 3:12:54 AM
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  • HAL Id : tel-03521631, version 1


Ander Movilla Miangolarra. Intracellular spatial organisation : The effects of non-ideal solutions. Physics [physics]. Université Paris sciences et lettres, 2021. English. ⟨NNT : 2021UPSLS076⟩. ⟨tel-03521631⟩



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