Tissue folding is a ubiquitous shape change event during development whereby a cell sheet bends into a curved 3D structure. This mechanical process is remarkably robust, and the correct final form is almost always achieved despite internal fluctuations and external perturbations inherent in living systems. While many genetic and molecular strategies that lead to robust development have been established, much less is known about how mechanical patterns and movements are ensured at the population level. I will describe how quantitative imaging, physical modeling and concepts from network science can uncover collective interactions that govern tissue patterning and shape change. Actin and myosin are two important cytoskeletal proteins involved in the force generation and movement of cells. Both parts of this talk will be about the spontaneous organization of actomyosin networks and their role in collective tissue dynamics. First, I will present how out-of-plane curvature can trigger the global alignment of actin fibers and a novel transition from collective to individual cell migration in culture. I will then describe how tissue-scale cytoskeletal patterns can guide tissue folding in the early fruit fly embryo. I will show that actin and myosin organize into a network that spans a domain of the embryo that will fold. Redundancy in this supracellular network encodes the tissue’s intrinsic robustness to mechanical and molecular perturbations during folding.

My lab studies the design principles of cytoskeletal materials the drive cellular morphogenesis, with a focus on contractile machinery in adherent cells. In addition to force generation, a key feature of these materials are distributed force sensors which allow for rapid assembly, adaptation, repair and disintegration. Here I will discuss our recent identification of 18 proteins from the zyxin, paxillin, Tes and Enigma families with mechanosensitive LIM (Lin11, Isl- 1 & Mec-3) domains. We developed a screen to assess the force-dependent localization of LIM domain-containing region (LCR) from ~30 genes to the actin cytoskeleton and identified features common to their force-sensitive localization. Through in vitro reconstitution, we found that the LCR binds directly to mechanically stressed actin filaments. Moreover, the LCR from the fission yeast protein paxillin-like 1 is also mechanosensitive, suggesting force-sensitivity is highly conserved. We speculate that the evolutionary emergence of contractile F-actin machinery coincided with, or required, proteins that could report on the stresses present there to maintain homeostasis of actively stressed networks.

My lab studies the design principles of cytoskeletal materials the drive cellular morphogenesis, with a focus on contractile machinery in adherent cells. In addition to force generation, a key feature of these materials are distributed force sensors which allow for rapid assembly, adaptation, repair and disintegration. Here I will describe how optogenetic control of RhoA GTPase is a powerful and versatile force spectroscopy approach of cytoskeletal assemblies and its recent use to probe repair response in actomyosin stress fibers. I will also describe our recent identification of 18 proteins from the zyxin, paxillin, Tes and Enigma families with mechanosensitive LIM (Lin11, Isl- 1 & Mec-3) domains that bind exclusively to mechanically stressed actin filaments. Our results suggest that the evolutionary emergence of contractile F-actin machinery coincided with, or required, proteins that could report on the stresses present there to maintain homeostasis of actively stressed networks.

Most materials deform when external stresses are applied. This paradigm is familiar to sculptors who deform clay to produce structures. However, living materials such as cells and embryos are capable of deforming on their own. Contractile active gels of the proteins actin and myosin are one of the main drivers of force generation in biology. Here I will present experiments that characterize the length-scale behavior of active gel contraction, which find evidence for critical behavior. I will then present experiments that characterize the dynamics of active gel contraction, which identify dynamic precursors to contraction.