Encoded biophysical information from actomyosin contractility can trigger discrete biochemical and cellular events
Abstract: Despite the importance of cell-cell adhesions, the molecular mechanisms of sensing, transducing, and adapting to mechanical signals at cell-cell adhesions are not fully understood, partly due to a lack of cell culture model and methods to mechanically manipulate tension at cell-cell contacts in an epithelial sheet. Here, we have established a cellular model to study the relationship between mechanical tension and cell-cell adhesion. We showed that MDCK kidney epithelial cells exhibit many contractile behaviors, including whole cell contractility, pulsatile centripetal junctional contractions, and ratchet and oscillating constrictions of apical junctional domain. By manipulating intercellular tension using a pressure chamber apparatus, we found that exogenously applied intercellular tension induces, in an amplitude, frequency, and duration-dependent manner, discrete cellular and biochemical events at cell-cell adhesions. One of these actomyosin-dependent processes driven by cyclic tension is the strengthening of cell-cell adhesion with concomitant recruitment of cell-cell adhesion proteins to cell-cell contacts. We showed that the strengthening of cell-cell adhesion is a result of sequential recruitment of tension-sensitive cell-cell adhesion proteins that eventually leads to the enhancement of the overall contractility of the epithelial sheet. Thus, two concepts have emerged from this study: (1) regulation of cell-cell adhesion by an iterative bi-partite mechanism with both biophysical and biochemical components and (2) a positive feedback mechanism to promote strengthening of cell-cell adhesion during epithelial maturation.
Bio
Vivian W. Tang received her bachelor degree from the University of California, Berkeley and her Ph.D. from the University of California, San Francisco. She received her postdoc training at Harvard Medical School. She joined the Department of Cell and Developmental Biology at the University of Illinois, Urbana-Champaign, in 2013.