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Single-Cell Biophysics: Measurement, Modulation, and Modeling
Monday Speaker Abstracts
34
Disruption of Cellular Force-sensing Triggers Systemic Tissue Collapse in the Botryllus
Vasculature
Megan Valentine
, Delany Rodriguez, Aimal Khankhel, Anthony DeTomaso.
University of California, Santa Barbara, CA, USA.
We recently discovered we can directly apply physical forces and monitor the downstream
responses in a living organism in real time through manipulation of the blood vessels of a marine
organism called Botryllus schlosseri. The extracellular matrix (ECM) plays a key role in
regulating vascular growth and homeostasis in Botryllus, a basal chordate which has a large,
transparent extracorporeal vascular network that can encompass areas >100 cm2. We have
shown that lysyl oxidase 1 (LOX1), which is responsible for cross-linking collagen, is expressed
in all vascular cells and is critically important for vascular maintenance. Inhibition of LOX1
activity in vivo by the addition of a specific inhibitor, ß-aminopropionitrile (BAPN), causes a
rapid, global regression of the entire vascular bed, with some vessels regressing >10 mm within
16 hrs. I will discuss the molecular and cellular origins of this systemic remodeling event, which
hinges upon the ability of individual vascular cells to sense and respond to mechanical signals,
while introducing this exciting new model system for cellular studies of mechanobiology.
Spontaneous Patterning of Cytoskeleton in Single Epithelial Cell Apicobasal Polarity
Formation
Chin-Lin Guo
.
Academia Sinica, Nankang, Taipei, Taiwan.
One important issue in developmental biology and regeneration medicine is how mammalian
cells spontaneously arrange themselves into specific, 3-D forms of organs. Loss of such ordering
is a hallmark of many diseases including cancer. To explain how such ordering emerges, for
decades, emphasis has been placed on spatial pre-patterning and multi-cellular coordination of
chemical signals. Not until rece1ntly, it is recognized that forces also play an important role in
the spatiotemporal ordering of multi-cellular architecture. For example, we have shown that cells
can use cell-matrix mechanical interactions to develop long-range multi-cellular coordination (up
to 600 microns) in tissue formation and cancer invasion. Here, we report that single epithelial
cells can spontaneously break symmetry and pattern cytoskeleton into a precursor form for
multi-cellular coordination including the formation of apicobasal polarity. Such process occurs in
the absence of spatial pre-patterning of chemical signals. Further, it provides a topological cue to
guide the spatial patterning of intracellular signals, which is absent in cancer cells, mesenchymal
cells, and stem cells. Through experimental and theoretical approach, we find that such
spontaneous patterning arises from the mechanical instability of microtubule and its interactions
with actin filaments, modulated by the stiffness of surrounding environment. Based on these
results, we propose that mechanical instability of single cells is sufficient to create a topological
precursor as a building block for chemical signaling and multi-cellular coordination in
development, and failure in such a process might lead to diseases.