Lipid droplets nucleate as neutral-lipid lenses between the two ER phospholipid leaflets at seipin-marked sites, then grow, coalesce, and shrink through three competing processes modelled here:
Ostwald ripening (Lifshitz–Slyozov–Wagner):
dr_i/dt = k_r · (1/r_c − 1/r_i)
r_c = Σr_i³ / Σr_i² (flux-weighted critical radius)
DGAT synthesis (adds TAG volume, biased to r > r_c):
dV_i/dt += k_s · w_i, w_i ∝ r_i²
ATGL lipolysis (surface reaction, blocked by perilipin coat):
dr_i/dt −= k_l · (1 − coverage_i)
- DGAT synthesis rate — triacylglycerol production feeding droplet growth from the ER; larger droplets absorb proportionally more new lipid (larger surface for esterification).
- ATGL lipolysis rate — the rate constant for adipose triglyceride lipase hydrolysing surface triglyceride to free fatty acid + diacylglycerol; it is a zero-order surface reaction, so shrink speed is independent of droplet size once uncoated.
- Perilipin coverage — PLIN-family proteins coating the droplet's phospholipid monolayer; higher coverage sterically blocks ATGL access, multiplying lipolysis by (1 − coverage).
- Seipin nucleation rate — how often new droplets bud from ER neutral-lipid lenses; new droplets start small and are the most vulnerable to ripening-driven shrinkage.
- Fasting pulse — briefly spikes lipolysis and strips perilipin coverage, mimicking hormone-sensitive PKA phosphorylation of perilipin during energy deficit that unmasks the droplet to ATGL/HSL (autophagic lipophagy proceeds through the same net shrinkage, delivering lipid to lysosomal acid lipase).
Because r_c is the volume-weighted mean radius, droplets above it keep growing while smaller ones lose lipid to them and eventually vanish — the same coarsening dynamic (Ostwald ripening) seen in emulsions, alloys, and every lipid droplet population under active turnover.