Weill Cornell Investigators Capture Near Atomic Resolution Images of TMEM16F Scramblase in Action

Weill Cornell researchers reveal the near-atomic structure of TMEM16F, a protein essential for blood clotting and bone development, using liposome technology.

By: AXL Media

Published: Apr 17, 2026, 8:11 AM EDT

Source: Information for this report was sourced from EurekAlert!

Solving a Structural Mystery in Cell Biology

Cell membranes are defined by a strictly organized bilayer of lipids, but many essential biological functions—from blood clotting to placenta formation—require this order to be intentionally disrupted. This task is performed by "scramblases," specialized proteins that flip lipids between the inner and outer layers of the membrane. For years, the specific mechanics of the human scramblase TMEM16F remained elusive because the protein’s complex structure tends to destabilize when removed from its natural environment. In a study published in Nature Structural and Molecular Biology, Dr. Alessio Accardi’s team at Weill Cornell Medicine successfully used artificial lipid capsules to stabilize and image the protein, finally catching the "scramblase in the act."

The X-Shaped Mechanism of Action

By utilizing low-temperature electron microscopy, the research team compared the active and inactive states of TMEM16F. They discovered that when high levels of calcium ions are present, subunits of the protein undergo a significant rotation, rearranging into an X-shaped configuration. This structural shift creates a distinctive groove or pore that penetrates the cell membrane. This change in shape has a dual effect: it thins the surrounding membrane to allow lipid molecules to be "scrambled" on the protein's exterior, while simultaneously opening an internal channel that allows small, charged ions like potassium or chloride to pass through.

Critical Roles in Blood Coagulation and Bone Health

The health implications of TMEM16F activity are profound. In platelet cells, the scrambling of lipids is the primary signal that triggers blood to clump and coagulate. Mutations that disable this protein lead to Scott Syndrome, a rare hemophilia-like bleeding disorder where patients cannot form effective clots. Beyond the blood, the protein is essential for bone development, immune response coordination, and the formation of the placenta during pregnancy. Conversely, when TMEM16F works abnormally or is hijacked by certain infections and cancers, it can lead to pathological complications, making it a high-priority target for drug developers.