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2. Jan. 2024
The membranes surrounding cells and their internal organelles have shapes full of folds and bulges, that are important for the proper function and interaction of organelles and cells with surroundings. The local shape is constantly changing as needed for different tasks, such as transporting material in and out. These hills and valleys are constantly forming on the membrane, but their formation is strictly regulated and monitored. Scientists from Masaryk University CEITEC in Brno have now discovered that a specific type of small protein is able to recognise membrane valleys that are associated with a "negative" membrane curvature. Until now, other small proteins were known to be sensitive only to "positive" (i.e., hills) membrane curvature. This discovery thus opens the door to applied research that benefits from a detailed understanding of cellular processes.
Cells have evolved specialised proteins and smaller peptides to recognize membrane curvature. These include amphiphilic helices (i.e., peptides with both a hydrophilic and a hydrophobic part), which are able to sense positive membrane curvature and accumulate in these regions. This behaviour of amphiphilic helices has been attributed to their ability to prefer the rearrangement of lipids in the positively curved parts of the membrane. However, scientists have now used computer simulations to show that peptides with the right composition can sense negative membrane curvature. The molecular origin of the curvature sensing is thus much more complex and, according to the authors, is related to the depth of peptide incorporation into the lipid membrane.
“We tested peptides with different compositions causing different depths of membrane insertion. We showed that these peptides can change their preference from positive to negative membrane curvature,” explains biophysicist Robert Vácha. “The knowledge that amphiphilic peptides are able to recognize not only positive but also negative membrane curvatures and understanding what causes these preferences gives us a new perspective on cellular proteins and their possible modifications,” adds co-author of the research Peter Pajtinka.
How these proteins detect the specific membrane shapes and curvatures may play an important role in cellular processes, such as the formation of vesicles needed for storage and transport of molecules within and across the cell, as well as in cell division or communication between cells.
Despite their miniature size, cells are still a major source of discoveries, pushing the boundaries of our knowledge and the possibilities of applied research. Scientists at CEITEC Masaryk University have been contributing to this trend for a long time.
The research was published in The Journal of Physical Chemistry Letters on 28 December 2023 and was funded by a grant from the European Research Council (ERC) and the National Institute of Virology and Bacteriology (NIVB).
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