Single-Cell Biophysics: Measurement, Modulation, and Modeling

Single-Cell Biophysics: Measurement, Modulation, and Modeling

Monday Speaker Abstracts

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.

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