Statistical physics of molecular sorting in living cells
Joint seminar with the Soft Matter group at LPS
Elisa Floris (Politecnico de Torino, Italy)
Molecular sorting is a fundamental process responsible for the organization of intracellular matter: biomolecules that dwell on the outer and inner membranes of the cell are partitioned into spatially localized domains and engulfed into small vesicles, that detach from the membrane to be delivered to their right destinations. A recently proposed theoretical model of this process is based on the coupling of a) phase-separation-driven formation of sorting domains and b) domain-induced membrane bending, leading to vesicle nucleation . In this minimal model, molecules are randomly inserted on the lipid membrane, can diffuse laterally and aggregate into domains, and are extracted as part of a domain once it has reached a characteristic extraction size, representing the average size of mature vesicles. The predictions of the theory and numerical investigations of a latticegas realization of the model show the existence of an optimal region of parameter space where sorting is most efficient. In the experiments, detected domains are commonly classified into two groups: productive domains, if their growth eventually terminates in the nucleation of a vesicle, and unproductive domains which rapidly dissolve. To interpret these data, we use central notions of the classical theory of phase separation, such as the boundary tension and the critical domain size. Comparison with experimental results shows that the statistical properties of productive and unproductive domains inferred from experimental data are in agreement with those predicted from numerical simulations of the model, compatibly with the hypothesis that molecular sorting is driven by a phase separation process. The model is further extended to account for the simultaneous sorting of a multiplicity of molecular species, revealing that, when keeping fixed the total incoming molecular flux, the average molecule residence time increases with the heterogeneity of the molecular pool according to a simple scaling law. Molecular sorting is further investigated by means of a simplified one-dimensional lattice-gas model, where the membrane is allowed to undergo the topological transformations corresponding to fusion and detachment of molecule-loaded vesicles.
 Marco Zamparo, Donatella Valdembri, Guido Serini, Igor V Kolokolov, Vladimir V Lebedev, Luca Dall’Asta, and Andrea Gamba. Optimality in self-organized molecular sorting. Physical Review Letters, 126(8):088101, 2021.