ARTIFICIAL CELLS TAKE THEIR STEPS : MOVABLE CYTOSKELETON MEMBRANE FABRICATED FOR THE FIRST TIME
Using only a few
ingredients, the biophysicist Prof. Andreas Bausch and his team at the
Technische Universität München (TUM) have successfully implemented a
minimalistic model of the cell that can change its shape and move on its own.
They describe how they turned this goal into reality in the current edition of
the journal Science, where their
research is featured as cover story
Cells are complex
objects with a sophisticated metabolic system. Their evolutionary ancestors,
the primordial cells, were merely composed of a membrane and a few molecules.
These were minimalistic yet perfectly functioning systems.
Thus, "back to
the origins of the cell" became the motto of the group of TUM-Prof.
Andreas Bausch, who is member of the cluster of excellence "Nanosystems
Initiative Munich (NIM)" and his international partners. Their dream is to
create a simple cell model with a specific function using a few basic
ingredients. In this sense they are following the principle of synthetic
biology in which individual cellular building blocks are assembled to create
artificial biological systems with new characteristics.
The vision of the
biophysicists was to create a cell-like model with a biomechanical function. It
should be able to move and change its shape without external influences. They
explain how they achieved this goal in their latest publication in Science.
The magic ball
The biophysicists'
model comprises a membrane shell, two different kinds of biomolecules and some
kind of fuel. The envelope, also known as a vesicle, is made of a
double-layered lipid membrane, analogous of natural cell membranes. The scientists
filled the vesicals with microtubules, tube-shaped components of the
cytoskeleton, and kinesin molecules. In cells, kinesins normally function as
molecular motors that transport cellular building blocks along the
microtubules. In the experiment, these motors permanently push the tubules
alongside each other. For this, kinesins require the energy carrier ATP, which
was also available in the experimental setup.
From a physical
perspective, the microtubules form a two-dimensional liquid crystal under the
membrane, which is in a permanent state of motion. "One can picture the
liquid crystal layer as tree logs drifting on the surface of a lake,"
explains Felix Keber, lead author of the study. "When it becomes too
congested, they line up in parallel but can still drift alongside each
other."
Migrating faults
Decisive for the
deformation of the artificial cell construction is that, even in its state of
rest, the liquid crystal must always contain faults. Mathematicians explain
these kinds of phenomena by way of the Poincaré-Hopf theorem, figuratively also
referred to as the "hairy ball problem." Just as one can't comb a
hairy ball flat without creating a cowlick, there will always be some
microtubules that cannot lay flat against the membrane surface in a regular
pattern. At certain locations the tubules will be oriented somewhat
orthogonally to each other -- in a very specific geometry. Since the
microtubules in the case of the Munich researchers are in constant motion
alongside each other due to the activity of the kinesin molecules, the faults
also migrate. Amazingly, they do this in a very uniform and periodic manner,
oscillating between two fixed orientations.
Spiked extensions
As long as the vesicle
has a spherical shape, the faults have no influence on the external shape of
the membrane. However, as soon as water is removed through osmosis, the vesicle
starts to change in shape due to the movement within the membrane. As the
vesicle loses ever more water, slack in the membrane forms into spiked
extensions like those used by single cells for locomotion.
In this process, a
fascinating variety of shapes and dynamics come to light. What seems random at
first sight is, in fact, following the laws of physics. This is how the
international scientists succeeded in deciphering a number of basic principles
like the periodic behavior of the vesicles. These principles, in turn, serve as
a basis for making predictions in other systems.
"With our
synthetic biomolecular model we have created a novel option for developing minimal
cell models," explains Bausch. "It is ideally suited to increasing
the complexity in a modular fashion in order to reconstruct cellular processes
like cell migration or cell division in a controlled manner. That the
artificially created system can be comprehensively described from a physical
perspective gives us hope that in the next steps we will also be able to
uncover the basic principles behind the manifold cell deformations."
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