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How stiff are lipid domains, and what forces align them?

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Ordered, cholesterol-rich membrane domains are about three times stiffer than disordered ones, and thermal wobbling of the floppier domains provides a large share of the repulsion between membranes.

Source

Bending Rigidities and Interdomain Forces in Membranes with Coexisting Lipid Domains

Kollmitzer B, Heftberger P, Podgornik R, et al. · Biophysical journal · 2015

doi.org/10.1016/j.bpj.2015.05.003Read the full paper ↗34 citationscc by

Study at a glance

Design
Other — X-ray scattering of osmotically stressed multilamellar vesicles (DOPC/DSPC/cholesterol) fitted by membrane-stack Monte Carlo simulations.
N
No participants; samples at a range of PEG osmotic pressures, analysed for coexisting Lo and Ld phases.
Population
Model lipid membranes with coexisting liquid-ordered (Lo) and liquid-disordered (Ld) domains
Outcome
Bending rigidity and parameters of hydration, van der Waals and undulation interactions between like domains

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

The researchers made stacks of lipid bilayers from a three-lipid mixture that separates into ordered and disordered domains, then squeezed them with polymer solutions of known osmotic pressure. X-ray scattering gave the water spacing and the size of membrane fluctuations for each phase. They fitted these data with Monte Carlo simulations of fluctuating membrane stacks, adjusting hydration strength, hydration decay length and bending rigidity, with the van der Waals strength calculated separately.

What they found

The bending rigidity was about 44 zJ for the disordered phase and 120 zJ for the ordered phase, a roughly threefold difference. Van der Waals attraction was almost the same for both phases, but the hydration force decayed over a noticeably shorter distance in the disordered phase and undulation repulsion was much stronger there. These differences cancel so that pressure-versus-spacing curves look nearly identical, showing why fluctuation data are needed to separate the forces.

The limits

What it doesn't show

The fit for the ordered phase was poorer than expected (reduced chi-squared of 6), which the authors attribute to the scattering theory breaking down for highly ordered, compressed samples. The van der Waals strength was estimated by treating the bilayers as pure hydrocarbon, a first-order approximation. Only one lipid composition was studied, and the reason for the different hydration decay lengths remains unexplained; the work also does not directly test a theory of domain alignment.

Key terms

Bending rigidity (Kc)
The energy cost of curving a membrane; higher values mean a stiffer membrane that fluctuates less.
Osmotic stress
Using a polymer solution that cannot enter between bilayers to apply a known pressure that pushes them together.
Hydration force
A short-range repulsion between membranes from structured water at their surfaces, decaying roughly exponentially.
Undulation (fluctuation) force
An entropic repulsion arising because thermally wobbling membranes lose freedom to fluctuate when brought close together.
Liquid-ordered / liquid-disordered phases
Coexisting fluid membrane phases; the ordered one is rich in saturated lipid and cholesterol and more tightly packed.

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Quiz yourself

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What is the main difference in stiffness between the two lipid phases?

Common questions

Why measure fluctuations and not just spacing?

The spacing-versus-pressure curves were almost identical for both phases, so only the fluctuation data could separate the different stiffnesses and forces.

Why use Monte Carlo simulation instead of a simpler formula?

Undulation and direct forces are coupled in a way that simple additive approximations miss, so the authors simulated the full fluctuating stack and fitted it to data.

Why is the ordered phase stiffer?

It contains more saturated lipid and about three times as much cholesterol, both of which stiffen the bilayer.

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