Did you know that almost all of the molecules that a cell makes have a certain handedness, and that all living organisms contain “one-handed” molecules? Handedness, or chirality, is a defining signature of life; NASA develops remote sensing instruments to detect homochirality (“one-handedness”) as a signature of extraterrestrial life.
How life came to be homochiral is a central problem in developing theories of life’s chemical origins. In a recent study in Nature Chemistry, scientists at UC Irvine and Scripps Research uncovered an interesting property of cell membranes that might provide clues as to how homochirality emerged on the early earth.
Membrane bilayers surround every living cell, controlling the passage of nutrients and wastes. They are made of lipids, which are also chiral. Some molecules, especially well-designed drugs, can slip through the membrane in a process call “permeation” to affect the cell’s functioning. Just as your left hand only fits in a left-handed glove, the researchers reasoned that chiral membranes might favor one chirality of molecule.
“Our experiments showed that chiral membranes are selectively permeable to one chirality of amino acid,” said UCI School of Pharmacy and Pharmaceutical Sciences Professor Brian Paegel, who led the study. “To our surprise, membranes built from biological chirality lipids were permeable to biological chirality amino acids. Primitive cell membranes might have been chirality amplifiers, setting the stage for homochirality in life.”
Making these permeability measurements was also a major challenge. UCI postdoctoral fellow and first author of the study, Dr. Juan Hu, engineered a device for high-speed assembly of synthetic membranes and permeability testing.
“Our microfluidic device generates a continuous train of droplets,” said Hu. “When the droplets touch, they form a synthetic bilayer. We could track the movement of chiral molecules between droplets in real time. It allows measurement of very rapid permeation.”
Membrane permeation is also important in drug development. Drugs that must reach a target protein inside the cell must first cross the membrane bilayer. Although many properties are known to cause a drug to permeate a membrane more efficiently, chirality is not one of them.
“Drug designers may now want to consider chirality,” Paegel said. Moving forward, Paegel says that the team will continue to investigate how chirality impacts pharmacokinetics, which is the absorption, distribution, metabolism, and excretion of molecules to better inform drug discovery.
“Chiral Lipid Bilayers are Enantioselectively Permeable” was published in the journal Nature Chemistry on June 10. Co-authors include Professor Donna Blackmond and Dr. Alexander Jones of Scripps Research and Dr. Wesley Cochrane of the Salk Institute.
Funding support came from the National Institutes of Health, the National Science Foundation, and the Simons Foundation Collaboration on the Origins of Life.