Biophysical Society Thematic Meeting| Aussois 2019

Biology and Physics Confront Cell-Cell Adhesion

Poster Abstracts

14-POS Board 14 RELATIONSHIP BETWEEN EPITHELIAL TUBE FORMATION AND MECHANICAL FORCES IN THREE-DIMENSIONAL ECM Hiroko Katsuno-Kambe 1 ; James Hudson 2 ; Alpha S Yap 1 ; 1 Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia 2 Medical Research Institute, QIMR Berghofer, Herston, Australia Tubular formation is a fundamental process in tissue development. In particular, epithelia tissues such as lung, mammary gland and kidney form multiple tubular structures to transport gases and liquids. However, it is still unclear how groups of cells determine the orientation axis of the overall tubular structures. Notably, recent studies suggest that the extracellular matrix (ECM) might be involved in patterning of tubular structures. To understand whether the ECM plays a role in tubular formation, we cultured epithelial cells in three-dimensional gels in vitro. When MCF10A epithelial cells are cultured in Matrigel, they formed acini structures. Interestingly, these cells formed both acini and cord-like structures when cultured in collagen gel. To understand whether the cord-like structures observed in collagen gel originated from acini structures, we harvested acini from Matrigel and transferred them into collagen gels. Remarkably, we found that acini began elongating in collagen gels. In addition, inhibition of actomyosin contractility perturbed acini elongation. These findings suggest that cellular contractility is pivotal for acini elongation. We therefore wondered how cellular contractility might influence symmetry breaking at the supracellular level of aggregates. We hypothesized that mechanical forces generated by cells might reorganize collagen fibers of the ECM. Using second harmonic generation microscopy, we found that collagen fibers are rearranged when acini elongate. Furthermore, application of a uniaxial stretch on collagen gels aligned fibers and acini elongated along the stretch axis even after the stretch was released. We hypothesize that acini can detect the axis of short-term stretch by recognizing the aligned fibers. In conclusion, these results highlight the potential relationship between mechanical forces and ECM reorganization in tubulogenesisis.

52