Lipid density governs cell flexibility

Lipid density has been shown to be the defining factor in membrane flexibility, potentially opening new avenues in synthetic biology.

Research into membrane behavior has revealed that how tightly lipids are packed into the membrane is the primary factor in determining their flexibility. The work, led by Rana Ashkar, Virginia Tech (VA, USA), has overturned the previous assumption that different types of lipids behave differently when exposed to cholesterol, shedding light on our understanding of homeostasis and other cellular functions.

A new perspective

Instead of using macroscopic measurements, as in previous research into membrane elasticity, Ashkar and her team utilized neutron spin–echo (NSE) and solid-state ²H nuclear magnetic resonance (NMR) spectroscopy to understand lipid chain conformations. Lipid packing densities were obtained by small-angle X-ray and neutron scattering (SAXS/SANS).

Once the mesoscopic bending moduli was determined, it was corroborated by Michael Brown’s lab at the University of Arizona (AZ, USA) and Milka Doktorova’s lab at Stockholm University (Sweden) utilizing all-atom molecular dynamics simulations.

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Ashkar discovered that cholesterol induces membrane thickening and tighter lipid packing while also stiffening saturated and unsaturated lipid membranes. Experimentally, the team demonstrated the bending moduli depended on lipid packing density and followed common biophysical scaling laws, regardless of chain unsaturation, cholesterol content or temperature.

“Membranes can have remarkable compositional complexity, but what really matters in determining or predicting their elasticity is how packed they are,” commented Ashkar. “And that is a very, very powerful design principle that cells seem to follow and that we can now apply in engineering lifelike artificial cells.”

From research to the real world

Ashlar and her team hope that this work will have significant real-world applications. In the paper, they suggest that “optimizing protein function and developing membrane-targeted therapeutics…[and] design of artificial cells with tunable biophysical properties and controlled function” could all now be possible.