Cell-like structures created in microfluidic circuit assembly line
15 March 2011
The Scripps Research Institute in Florida has built a
microscopic assembly line that mass produces synthetic cell-like
The new computer-controlled system represents a technological
leap forward in the race to create the complex membrane structures
of biological cells from simple chemical starting materials.
While most cellular components such as genes or proteins are
easily prepared in the laboratory, little has been done to develop a
method of synthesizing cell membranes in a uniform, automated way.
Current approaches are capricious in nature, yielding complex
mixtures of products and inefficient cargo loading into the
resultant cell-like structures.
The new technology transforms the previously difficult synthesis
of cell membranes into a controlled process, customizable over a
range of cell sizes, and highly efficient in terms of cargo
The membrane that surrounds all cells, organelles and vesicles —
small subcellular compartments — consists of a phospholipid bilayer
that serves as a barrier, separating an internal space from the
The new process creates a laboratory version of this bilayer that
is formed into small, cell-sized compartments.
How it works
A microfluidic circuit generates water droplets in
lipid-containing oil. The lipid-coated droplets travel down one
branch of a Y-shaped circuit and merge with a second water stream at
the Y-junction. The combined flows of droplets in oil and water
travel in parallel streams toward a triangular guidepost.
Then, the triangular guide diverts the lipid-coated droplets into
the parallel water stream as a wing dam might divert a line of small
boats into another part of a river. As the droplets cross the
oil-water interface, a second layer of lipids deposits on the
droplet, forming a bilayer.
The end result is a continuous stream of uniformly shaped
cell-like compartments. The newly created vesicles range from 20 to
70 micrometers in diameter — from about the size of a skin cell to
that of a human hair. The entire circuit fits on a glass chip
roughly the size of a poker chip.
The researchers also tested the synthetic bilayers for their
ability to house a prototypical membrane protein. The proteins
correctly inserted into the synthetic membrane, proving that they
resemble membranes found in biological cells.
“Biology is full of synthetic targets that have inspired chemists
for more than a century,” said Brian Paegel, Scripps Research
assistant professor and lead author of a new study published in the
Journal of the American Chemical Society. “The lipid membrane
assemblies of cells and their organelles pose a daunting challenge
to the chemist who wants to synthesize these structures with the
same rational approaches used in the preparation of small
“Membranes and compartmentalization are ubiquitous themes in
biology,” noted Paegel. “We are constructing these synthetic systems
to understand why compartmentalized chemistry is a hallmark of life,
and how it might be leveraged in therapeutic delivery.”
Sandro Matosevic and Brian M. Paegel. Stepwise Synthesis of
Giant Unilamellar Vesicles on a Microfluidic Assembly Line. Journal
of the American Chemical Society, 133
(9), pp 2798–2800: February 10, 2011.