arXiv subjects

Damiano Andreghetti

Publications and source records attributed to Damiano Andreghetti.

3 recordsLinked to original sources

arXiv2026

Speed-quality tradeoff in a physical model of molecular sorting

Eukaryotic cells rely on membrane-mediated processes to compartmentalize biomolecules, counteracting diffusion-driven homogenization. These processes involve the selective sorting and packing of molecules into lipid vesicles, which are then dispatched to appropriate intracellular destinations. Previous works introduced an abstract statistical physics framework for studying this molecular distillation process, where the membrane was treated as static and the focus was on molecular aggregation and extraction. Here, we extend this framework to explicitly incorporate dynamic membrane behavior, including bending, curvature generation, and changes in membrane size due to vesicle fusion and fission events. Sorting domains drive membrane curvature, leading to vesicle formation, detachment, and a molecular distillation process that alters membrane size. Using mesoscopic modeling and numerical tools, we investigate the resulting interplay between membrane mechanics and molecular sorting. We determine a well-defined parameter region where vesicle fission and efficient molecular sorting occur, controlled by membrane rigidity, spontaneous curvature, and pressure difference across the membrane. We further identify a trade-off between speed and quality of molecular distillation: parameters that accelerate vesicle formation tend to reduce the quality of distillation, and vice versa. We propose maximization of the rate of negative entropy production as a natural criterion to optimally balance these competing effects. In this context, optimal parameters emerge naturally from the coupled dynamics of molecular aggregation and membrane mechanics, suggesting a possible strategy for cellular sorting systems to strike an efficient balance between rapid vesicle formation and high sorting quality.

cond-mat.soft↗

arXiv2026

Enzyme-driven phase separation

The formation of polarized signaling domains on cell membranes is a fundamental example of biological pattern formation. While such patterns resemble structures from equilibrium phase separation, they are intrinsically non-equilibrium, driven by energy-consuming enzymatic cycles that switch molecules like phosphoinositides or small GTPases between distinct states. Here, we develop a minimal model of this enzyme-driven phase ordering process. Starting from microscopic reaction kinetics, we derive a mesoscopic theory that belongs to the class of active Model A with a global constraint. This framework yields an explicit mean-field phase diagram and closed-form expressions for key observables, such as interfacial tension, domain fractions, and phase coexistence boundaries, in terms of kinetic rates. In this context, phase coexistence is controlled by non-equilibrium parameters like catalytic rates and enzymatic asymmetry, rather than equilibrium parameters such as saturation concentrations. The resulting phase-separated domains rapidly exchange material with their surroundings. Their maintenance requires a continuous power input determined by enzymatic kinetics. The predicted phenomenology is consistent with experimental observations on reconstituted systems of phosphoinositide and Rab5 membrane patterning. We further study how metastable uniform states decay via nucleation of minority-phase domains and subsequent coarsening, driven by an effective interfacial tension. Using large deviation theory, we derive the critical nucleation radius under the action of the intrinsic, multiplicative chemical noise. The analytical results are quantitatively confirmed by stochastic simulations of the process. Our work provides a theoretical framework identifying key biochemical parameters controlling active phase separation on membrane scaffolds, offering testable predictions for experiments.

physics.bio-ph↗

arXiv2025

Molecular sorting on a fluctuating membrane

Molecular sorting in biological membranes is essential for proper cellular function. It also plays a crucial role in the budding of enveloped viruses from host cells. We recently proposed that this process is driven by phase separation, where the formation and growth of sorting domains depend primarily on direct intermolecular interactions. In addition to these, Casimir-like forces -- arising from entropic effects in fluctuating membranes -- may also play a significant role in the molecular distillation process. Here, using a combination of theoretical analysis and numerical simulations, we explore how Casimir-like forces between rigid membrane inclusions contribute to sorting, particularly in the biologically relevant regime where direct intermolecular interactions are weak. Our results show that these forces enhance molecular distillation by reducing the critical radius for the formation of new sorting domains and facilitating the capture of molecules within these domains. We identify the relative rigidity of the membrane and supermolecular domains as a key parameter controlling molecular sorting efficiency, offering new insights into the physical principles underlying molecular sorting in biological systems.

physics.bio-ph↗