3-D Topological Arrangement of Cytoskeleton Modulated by Environmental Mechanics
Chiao-Yu Tseng1*, Chin-Lin Guo1, Emilio Sanchez1
1Physics, Academia Sinica, Taipei, Taiwan
* presenting author:Chiao-Yu Tseng, email:tsengc@gate.sinica.edu.tw
In developmental biology and regenerative medicine, one important and long-lasting issue is to understand how mammalian cells spontaneously arrange themselves into specific, 3-D forms of organs. Loss of such ordering is a hallmark of many diseases including malformation and cancer. For decades, emphasis has been placed on spatial pre-patterning and multi-cellular coordination of chemical signals, to explain how such ordering emerges. Not until rece1ntly, it is recognized that forces also play an important role. We have, for example, shown that cells can develop long-range multi-cellular coordination (up to 600 microns) in tissue formation and cancer invasion, through cell-matrix mechanical interactions. Here, we report that single epithelial cells can spontaneously break symmetry and partition cytoskeleton into the precursor forms for multi-cellular coordination including the formation of apicobasal polarity, in the absence of pre-patterning of intracellular or extracellular chemical signals. Furthermore, such process provides geometrical cues to guide the spatial patterning of intracellular signals and extracellular matrix molecules. It is specific to normal epithelial cells and not observed in several cancer cell lines, mesenchymal cells, or stem cells. Through manipulating environmental mechanics and mathematical modeling, we find that the spontaneous partition of cytoskeleton arises from the mechanical instability in the counteracting between actomyosin contraction and microtubule buckling, and is modulated by substrate rigidity. 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.

Keywords: Biophysics, Cytoskeleton , Environmental Mechanics