New research out of the University of North Carolina’s Freeman Lab and Nazockdast Lab has pioneered a method of anchoring synthetic peptides that will be able to instruct shape changes of lipid membranes and provide a key feature for functional, self-sustaining synthetic cells of the future.

Part hydrophobic, part hydrophilic peptide strands are introduced to a cell. Depending on the existing curvature of the cell, the peptides will imbed into the outer layer of the cell – the lipid bilayer – where it finds an escape from the watery environment. The number of strands able to find a place to burrow into depends on the curve of the cell.

Imagine a coiled spring like a Slinky and you want to fit a straw between the coils. If the spring is compressed together in a straight row, the coils are too close for the straw to fit between them. If you meet the opposite ends together to form a circle, the coils will be too far apart, and the straw will just fall through. So, there is a Goldilocks zone of where the coils are just far enough apart for the straw to fit and hold between them.

This is how the peptide settles into a gap in the lipid bilayer – the lipid bilayer is an array of molecules that encapsulate the cell. It is called a bilayer because it is represented as two lipid molecules with hydrophobic ‘tails’ between them. It is this tail area that our peptide wants to burrow to get out of the water.  

Just like the coils of a Slinky, when the lipid bilayer curves, there is separation in the lipid molecules. The more dramatic the curve, the more space comes between them. Too little, and the peptide cannot fit. Too much and there is too much separation and the hydrophobic sections cannot find a place to escape the water. It needs just the right space. Once burrowed, it anchors with protruding spurs.

The peptides can be created with different configurations so that certain areas like water and certain do not. Depending on this, different sections of the peptide will burrow into the bilayer. This anchoring technology and the variations it provide, will pave the way to change the shape of synthetic cells as desired – thus dictating the function of what the cell might do, such as move, produce molecules, and divide.

The full research, conducted by Christopher J. Edelmaier, Stephen J. Klawa, S. Mahsa, Qunzhao Wang, Shreeya Bhonge, Ellysa J.D. Vogt, Brandy N. Curtis, Wenzheng Shi, Sonya M. Hanson, Daphne Klotsa, M. Gregory Forest, Mofidi, Amy S. Gladfelter, Ronit Freeman , Ehssan Nazockdast is available through the Biophysical Journal, April 02, 2025.

Read the full paper here:

Charge distribution and helicity tune the binding of septin’s amphipathic helix domain to membranes: Biophysical Journal