Cell membranes cradle, protect, and gatekeep living cells. Membranes can even affect how a cell behaves.
But membranes' own erratic behavior has puzzled scientists for years.
Turns out, it's all about perspective: When physicist Rana Ashkar's team members looked at how membranes behave on the nanoscale, they were able to identify unified biophysical laws that membranes have adhered to all along.
Published in Nature Communications , these findings have significant implications for disease intervention methods, drug delivery applications, artificial cell technologies, and the next phase of membrane biophysics.
Composition-shifting superheroes
Primarily composed of fatty compounds called lipids, membranes are highly adaptive. They can change their lipid composition in response to environmental factors, responding — sometimes in mere hours — to changes in diet, pressure, or temperature. This property, called homeostasis, keeps the cities of your cells humming along happily under different conditions.
To understand how homeostasis works, scientists have been trying to frame it within the context of an important physical principle that says the structure of the membrane must affect its physical properties.
Makes sense, right? What something is made of must impact how it behaves.
And yet, for years, membranes obstinately evaded this law.
Disregard of the law was on full display when scientists injected cholesterol into model cell membranes, changing the structure, to see if it would affect a membrane's property, such as its flexibility or elasticity. Results were all over the board — some membranes stiffened while others didn't.
It's not the type of lipid but how you pack it
"It caused a dilemma in the field," Ashkar said. "Somehow cholesterol changed the structure of some membranes but not their elastic properties."
The widespread assumption was that different types of lipids reacted differently to cholesterol. But Ashkar wasn't convinced. She decided to try something else. Previous studies looked at membrane elasticity using macroscopic measurements. Ashkar's team looked closer. Much closer.
Using neutrons and X-rays, team members found that what affects elasticity isn't the type of lipid but how tightly packed they are within the membrane.
Certain types of lipids resist being crowded, while others can get shoved in as tight as sardines. And the packing density is the primary factor that affects the flexibility of the membrane, which in turn regulates cell viability.
To further confirm these findings, Ashkar and her team collaborated with Michael Brown's lab at the University of Arizona and Milka Doktorova's lab at Stockholm University. Their nuclear resonance experiments and computational studies followed the same laws obtained by the Ashkar lab.
"Membranes can have remarkable compositional complexity, but what really matters in determining or predicting their elasticity is how packed they are," said 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."
Original study : DOI 10.1038/s41467-025-62106-0
