Lecturer: Dr. Inbal Hecht
Affiliation: School of Physics and Astronomy
Tel Aviv University
Abstract:
Migrating cancer cells exhibit various motility
modes, which differ in cell shape dynamics as
well as cell-environment and cell-cell
interactions. Cellular blebbing is involved in
amoeboid motility, an important motility mode
which is in the focus of current research. Blebs
are large, unstable membrane structures that
are driven by hydrostatic pressure and occur
when the cell cortex is ruptured or disconnects
from the plasma membrane. Blebbing occurs in
different cell types during apoptosis,
development and migration, and are related to
specific signaling in the cell, although the exact
mechanism is still barely understood.
We study different aspects of cellular blebbing
in general and in cancer metastasis in
particular. We use a mathematical model and
computer simulations to compare different
retraction mechanisms and signaling
components and their roles in bleb initiation
and retraction. A newly developed algorithm is
used to analyze experimental results and
automatically measure bleb characteristics.
Our new hybrid algorithm combines image
analysis with physical considerations and can
be applied to a variety of microscopy images,
from intercellular compartments to multi-
cellular colonies.
Amoeboid motility enables migration even
under metabolic or environmental stress.
However, it is more vulnerable to barriers in
the physical microenvironment. By analyzing
simulation results of group motility, we show
that a small population of mesenchymal cells
can enhance the migration of the amoeboid
cells as well. Cell-cell interaction, as evident for
example in hybrid epithelial-mesenchymal
cells, is only beneficial under metabolic stress.
We therefore predict that cell-cell adhesion
should be regulated as a stress-response
mechanism. Our findings are in agreement
with experimental results of migrating cancer
cells.