Authors: Scocozza, Bruno
Title: Collective information processing in synthetic morphogenic liposomes and hybrid cell-computer wound healing with optogenetically emulated signaling
Language (ISO): en
Abstract: Throughout the different scales at which living organisms operate, it is the collective behaviour between the entities that compose them that determines their identity and function. Biomolecules, cells and whole organisms interact to process information and generate organization at the subcellular, tissue and ecosystem scales. In the first part of this thesis, we investigated fundamental principles of cellular morphogenesis in response to external cues in a Synthetic Morphogenic Membrane System (SynMMS). SynMMS was composed of an encapsulated dynamic microtubule (MT) aster, together with a light-inducible signal transduction system in cell-sized liposomes. We show that light-activated signaling induces MT growth through activation of an activity gradient of the MT-regulator stathmin. SynMMSs are thus capable of responding to local external light cues with directed morphological changes, as if originating from an extracellular morphogen. Morphometric analysis methods enabled us to uncover feedbacks within and among the signaling and cytoskeletal subsystems, which are mediated by the deformable membrane. We found that bidirectional interactions between the signaling and MT-aster system underlie the creation of self-organized morphologies as well as their reorganization in the direction of external light cues. In the second part, we develop a novel method to investigate how at a higher scale, the coupling of such intracellular processing networks leads to functional collective behaviour. We develop a hybrid cell-computer experimental interface to create hybrid wound healing assays, in which living cells are recruited to a virtual wound while undergoing virtual paracrine signaling. The migration state of cells is measured in real time from which in silico cell-to-cell communication is computed and translated into optogenetic actuation that induces cell migration, emulating extracellular signaling cues. The hybrid assay phenocopies features of in vivo neutrophil swarming towards an injury, demonstrating that a paracrine signaling relay allows expanding the recruitment region. Thus, this method allows to create hybrid in vitro-in silico dynamics where the influence of intercellular communication parameters can be quantitatively investigated. Altogether, investigation of collective behaviour in synthetic proto-cells uncovered how MTsignaling interactions determine cellular morphogenesis, while hybrid cell-computer interfaces establish a new method for quantitative interrogation of cellular communication during tissue morphogenesis.
Subject Headings: Cell-computer interface
Wound healing
Hybrid assays
Subject Headings (RSWK): Morphogenese
Issue Date: 2020
Appears in Collections:Chemische Biologie

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