Study sheds light on lipid asymmetry in cell membranes

BUFFALO, N.Y. – In cell biology, the membrane is made of two layers of lipids that are often unevenly distributed. Scientists know this asymmetry affects how membranes perform important tasks like forming protective barriers and enabling communication with other cells.

What’s less clear, however, is how this lack of uniformity changes the membrane’s physical properties such as its structure and flexibility.

A new computational study led by University at Buffalo scientists and published April 21 in Biophysical Journal sheds light on this understudied area. The research suggests that cells may use the asymmetric positioning of lipids as a tuning mechanism to control membrane stiffness, dynamics and other properties.

“Our findings uncover a direct link between asymmetry and structure,” says corresponding author Xin Yong, PhD, associate professor in the Department of Mechanical and Aerospace Engineering. “They show how cells precisely control membrane properties to regulate communication, transport materials, and adapt to stress.”

Yong and UB PhD candidate Emad Pirhadi relied on UB supercomputers to model multiple types of membrane systems, including those very simple and very complex. As they increased asymmetry, they measured how structure, flexibility and lipid organization changed.

Among the more interesting results:

• Low- to moderate levels of asymmetry caused small, transient gel-like patches of tightly clustered lipids to form and dissipate in an otherwise fluid membrane.
• The transient gels made the membrane softer and more flexible, which in turn make the membrane more responsive to the cell’s needs.
• But as asymmetry increases, the gel-like patches become more stable, which leads the membrane to become more rigid.
• The gel-like areas tend to cluster in areas of the membrane that curve outward, while the fluid regions prefer inward areas.

“The findings help explain how membranes still carry out their essential tasks while also adapting to changes,” says Pirhadi.

The work, supported by grants from the National Science Foundation and the National Institutes of Health, could have implications in cell biology, biophysics, pharmacology, microbiology, biomedical engineering and other fields.