BGU and Weizmann Institute of Science researchers have disproved an old
model of how actin filaments in cells generate waves while offering a distinct
framework that goes beyond the basic understanding of functionality and offers
new strategies that might eventually be relevant to cancer detection and treatment.
Their research was
published today in Nature Communications, which is one of the top
three most important journals for multi-disciplinary research such as this one,
which combined mathematics, biophysics and experimental biology.
Actin filaments are one
of the fundamental components of the soft and dynamic skeleton of cells and
also play a key role in the reshaping of cell morphologies and cellular
motility. The formation of actin filaments manifests in visible cup-shaped
ruffles (waves) on the surface and throughout the cell, a behavior that is also
known as macropinocytosis,
whereby cells produce vesicles that are absorbed into the cell. According to
current understandings, such circular waves have a two-fold purpose: to take up
large molecules (e.g., nutrients) that the cell needs, but cannot acquire
through its ion channels, and to “reset” the cell by disordering the actin infrastructure,
i.e., an efficient softening mechanism of the cytoskeleton. The waves also
concentrate membrane receptors into the vesicles, allowing cells to respond to
external chemical signals.
until now that the waves were to be attributed to a pulse-like motion similar
to the electrical pulses (action potentials) in nerves. However, Dr. Arik Yochelis (BGU), Prof. Nir Gov (Weizmann) and their postdoctoral fellow Dr. Erik Bernitt
(Germany) discovered by carefully revisiting these experimentally observed
waves that the mathematical description of the pulse assumption mechanism did
not fit. Instead, these membrane ruffles belong to a distinct class of generic
dynamic behavior: wave-fronts, the wave serves as a propagating wall connecting
high and low actin concentrations. They built a robust model that not only
reproduces the wave behavior but also qualitatively predicted new dynamic
behavior that, surprisingly, has also been found in experiments. Thus their
approach opens up new possibilities for many future applications, including
Previous studies in
cancer research have implied that deviation from the regular wave dynamics
correlates with promotion of cancerous phenotypes, i.e., in cases where these
actin-driven waves get damaged or their dynamics are suppressed. In addition,
is an important mechanism of nutrient uptake and receptor recycling in tumor
cells, and therefore understanding it better could shed light on its role in
cancer cell migration.
“Now that we have a much
clearer understanding of these waves, if we can control their dynamics, then
theoretically we could assist in preventing and/or identifying pathways toward
and about cancer cells that up to now were overlooked,” say Yochelis and Gov.
Dr. Erik Bernitt was a
visitor at the Weizmann Institute of Science during this collaborative project.
Another co-author is Prof. Hans-Günther Döbereiner of Bremen University, who
was Dr. Bernitt’s Ph.D. supervisor, and in whose lab the experiments were
The study received
funding from the Adelis Foundation, Ministry of National Infrastructures,
Energy and Water Resources of Israel, and the German Academic Exchange Service.
“Fronts and waves of
actin polymerization in a bistability-based mechanism of circular dorsal
Hans-Günther Döbereiner, Nir S. Gov & Arik Yochelis
Figure 1 | Characteristics of CDRs. (a)
Time-lapse sequence showing the typical course of a spontaneously formed CDR
(scale bar: 25 mm). The white arrow indicates the initiation of the CDR and the
red arrow the macropinosomes (appearing as white spots) formed on CDR collapse.
(b) Living cell stained for f-actin with a
close-up view on a CDR wavefront showing its sub-structure of dynamic actin
clusters (scale bars: full image 25 mm, close-up 5 mm).
(c) Kymographs along red lines in normal (n) and
tangential (t) direction to the CDR in b, highlighting the rapid actin turnover
within CDR wavefronts.
(d) Actin organization of a cell exhibiting two
CDRs imaged with confocal fluorescence microscopy in two different z-positions.
(e) Close-up view of the vertically integrated
intensity of the region of interest highlighted with a white rectangle in d.
(f) Profile of fluorescence intensity sampled along
a cut through the wavefront (white line in (e), length: 25 mm) showing the
state of wavefront exterior (P 0) and wavefront interior (P 1 þ ).