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Modulation of Liquid–Liquid Phase Separation of Poly-L-lysine Coacervates by Sodium Caprate: A Coarse-Grained Molecular Dynamics Study

Terrmin

HT25

Beskrivning

Aim
To investigate how sodium caprate (C10), a membrane permeability enhancer, modulates the formation, structure, and dynamics of poly-L-lysine-based liquid-liquid phase-separated systems using coarse-grained molecular dynamics simulations.

Background
Liquid–liquid phase separation (LLPS) of charged polyelectrolytes like poly-L-lysine (pLys) gives rise to coacervates—dense, membrane-less droplets with biological and technological significance. A recent study by Tsanai et al. (2021) demonstrates that Martini 3 coarse-grained molecular dynamics can reproduce key LLPS behavior, including salt-dependent phase transitions, water and ion partitioning, and molecular diffusion. Sodium caprate (C10), a short-chain fatty acid widely studied for its ability to enhance epithelial permeability, may alter coacervate properties through interfacial or hydration effects. However, its role in modulating LLPS, particularly in systems rich in poly-L-lysine, remains uncharted.

My Task
Construct coarse-grained models of sodium caprate (C10) compatible with the Martini 3.0 force field.
Set up and simulate coacervate systems based on poly-L-lysine/polyanion mixtures at varying salt and polymer concentrations, with and without C10.
Analyze how C10 affects phase separation thresholds, interfacial tension, and internal structure of poly-lysine-rich coacervates.
Quantify ion and water distribution and diffusion in coacervate vs. dilute phases.
Explore the partitioning behavior of small solutes (e.g., oligonucleotides or drugs) into poly-lysine coacervates in the presence of C10.

Expected Results
Determination of whether C10 localizes at coacervate interfaces or integrates into the dense phase.
Identification of shifts in the LLPS threshold or morphology of poly-L-lysine coacervates due to C10.
Changes in water and ion dynamics, suggesting altered coacervate permeability or hydration.
New insight into the potential of combining poly-lysine LLPS systems with fatty acid enhancers for applications in drug delivery or protocell models.

Huvudområde

Läkemedelsutveckling

Ämne

Läkemedelsformulering och Molekylär galenisk farmaci

Typ

Beräkningsstudie

Företag

Uppsala University

Ort/Plats

Uppsala

Handledarens namn

Per Larsson, Shahina Akter

Handledarens e-post

per.r.larsson@uu.se

Institution

Institutionen för farmaci

Program

Masterprogram i läkemedelsmodellering

Kurs

Degree Project in Pharmaceutical Modelling within Pharmaceutics and Biopharmaceutics 45 c - 3FG001

Omfattning/hp

45hp