Curated Optogenetic Publication Database

Abstract: The active regulation of tissue material properties via phase transitions is central in morphogenesis. Transitions occur abruptly at critical points in different control parameters, such as cell density, shape or adhesion. Whether these parameters are interdependent, and perform redundant or distinct functions, is unknown. Here we show that depending on the co-regulation of multiple control parameters, a tissue not only tunes its deformability but also its morphogenetic trajectory. We theoretically define a phase diagram capturing the material states of zebrafish pluripotent tissues undergoing epiboly-a tissue movement occurring during gastrulation-and show that they simultaneously cross critical points in cell density, connectivity and adhesion strength. We then combine optogenetics, biophysical measurements and quantitative morphometrics to independently modulate each parameter in vivo, and identify adhesion as the main determinant of tissue rheology. Further decoupling adhesion from density and inducing adhesion-driven rigidification in unjammed pluripotent tissues is sufficient to switch their morphogenetic program and trigger epithelial organization. This switch in tissue reorganization is achieved via tricellular junction formation, followed by lumenogenesis and the initiation of apical polarity. Our work reveals that the nonlinear dynamics of emergent tissue mechanics are mechanisms of tissue organization and morphogenesis.

Abstract: The nuclear pore complex regulates nucleocytoplasmic transport. It was recently shown that the global mechanical stability of proteins regulates their nuclear import rate. On the basis of these findings, we hypothesize that the main principles governing protein translocation through narrow biological pores-in which locally unstructured and unfolded regions determine cargo orientation and translocation kinetics-can help rationalize protein trafficking across the nuclear pore complex. Inspired by single-molecule studies showing that proteins exhibit different mechanical stability when pulled from different termini, here we show that the rate of both nuclear import and export is enhanced when the translocating protein is threaded through the nuclear pore from the specific region exhibiting lower local nanomechanical stability and increased structural disorder. We demonstrate this for a range of model proteins with different folds and stabilities by combining single-molecule magnetic tweezers with single-cell optogenetic experiments, complemented by steered molecular dynamics simulations and biochemical binding assays. Our bioinformatics survey then shows that in human transcription factors, the termini containing the nuclear localization signal sequence exhibit a higher degree of structural disorder. We propose that protein orientation might offer an additional layer of structural and mechanical control of the kinetics of nuclear transport.