Cholesterol modulates membrane elasticity via unified biophysical laws

Teshani Kumarage, Sudipta Gupta, Nicholas B. Morris, Fathima T. Doole, Haden L. Scott, Laura-Roxana Stingaciu, Sai Venkatesh Pingali, John Katsaras, George Khelashvili, Milka Doktorova (), Michael F. Brown () and Rana Ashkar ()
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Teshani Kumarage: Virginia Tech
Sudipta Gupta: Virginia Tech
Nicholas B. Morris: Virginia Tech
Fathima T. Doole: University of Arizona
Haden L. Scott: Oak Ridge National Laboratory
Laura-Roxana Stingaciu: Oak Ridge National Laboratory
Sai Venkatesh Pingali: Oak Ridge National Laboratory
John Katsaras: Oak Ridge National Laboratory
George Khelashvili: Weill Cornell Medical College
Milka Doktorova: Stockholm University
Michael F. Brown: University of Arizona
Rana Ashkar: Virginia Tech

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Cholesterol and lipid unsaturation underlie a balance of opposing forces that features prominently in adaptive cell responses to diet and environmental cues. These competing factors have resulted in contradictory observations of membrane elasticity across different measurement scales, requiring chemical specificity to explain incompatible structural and elastic effects. Here, we demonstrate that – unlike macroscopic observations – lipid membranes exhibit a unified elastic behavior in the mesoscopic regime between molecular and macroscopic dimensions. Using nuclear spin techniques and computational analysis, we find that mesoscopic bending moduli follow a universal dependence on the lipid packing density regardless of cholesterol content, lipid unsaturation, or temperature. Our observations reveal that compositional complexity can be explained by simple biophysical laws that directly map membrane elasticity to molecular packing associated with biological function, curvature transformations, and protein interactions. The obtained scaling laws closely align with theoretical predictions based on conformational chain entropy and elastic stress fields. These findings provide unique insights into the membrane design rules optimized by nature and unlock predictive capabilities for guiding the functional performance of lipid-based materials in synthetic biology and real-world applications.

Date: 2025
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DOI: 10.1038/s41467-025-62106-0

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