ED Sciences Chimiques
Light-responsive coacervate droplets as bio-inspired compartments
by Edison JIMENEZ GRANDA (Centre de Recherche Paul Pascal)
The defense will take place at 9h30 - Amphiteatre Centre de recherche paul pascal, 115 Avenue du Dr Albert Schweitzer, 33600 Pessac
in front of the jury composed of
- Dora TANG - Professeure - Universität des Saarlandes - Rapporteur
- Nicolas GIUSEPPONE - Professeur - Institut Charles Sadron - Rapporteur
- Nicolas MARTIN - Chargé de recherche - Centre de recherche paul pascal - CoDirecteur de these
- Olivier MONDAIN-MONVAL - Professeur - Centre de recherche paul pascal - Examinateur
This thesis explores the potential of liquid-liquid phase separation (LLPS) as a foundational strategy for constructing membrane-free compartments that emulate essential cellular functions. The focus lies on light-responsive coacervate systems formed through the self-assembly of azobenzene-based amphiphiles with charged biomolecules such as nucleotides and polyelectrolytes. By systematically varying the chemical structure of these molecules, the study elucidates how factors such as charge valency and molecular architecture govern droplet formation, stability, and responsiveness to external stimuli, particularly light. Generally, lower-charged azobenzenes yield dynamic and reversible systems, whereas highly charged analogs form more stable but less responsive assemblies. Building upon these findings, the work investigates the integration of these azobenzene-based coacervates with classical polyelectrolyte systems, leading to the emergence of hierarchically organized, multiphase droplets. These structures exhibit reversible light-induced transitions, enabling spatial and temporal control over compartmentalization and molecular uptake. In this context two distinct photomodulation mechanisms were identified: (1) light-induced homogenization of multiphase droplets, and (2) light-triggered phase separation that transforms initially homogeneous droplets into compartmentalized architectures with emergent molecular selectivity. The thesis also introduces interchangeable coacervate systems wherein droplet phase identity can be toggled by light exposure. Using ternary mixtures of azobenzene amphiphiles and different polyelectrolytes, the systems display distinct physicochemical properties and encapsulation behaviors, as characterized by spectroscopy, fluorescence microscopy, and microfluidic encapsulation. Altogether, this work establishes a chemically defined, modular, and optically controllable platform for the design of synthetic LLPS-based compartments. These systems hold significant promise for applications in synthetic biology, origin-of-life studies, and the development of adaptive soft materials, while also highlighting key challenges such as precise control over phase dynamics, molecular selectivity, and hierarchical organization in future artificial cell engineering.