Dynamics of epithelial monolayers has recently been interpreted in terms of a jamming or rigidity transition. How cells control such phase transitions is, however, unknown. Here we show that RAB5A, a key endocytic protein, is sufficient to induce large-scale, coordinated motility over tens of cells and ballistic motion in otherwise kinetically-arrested monolayers. This is linked to increased traction forces and to the extension of cell protrusions, which align with local velocity. Molecularly, impairing endocytosis, macropinocytosis or increasing fluid efflux abrogates RAB5A-induced collective motility. A simple model based on mechanical junctional tension and an active cell reorientation mechanism for the velocity of self-propelled cells identifies regimes of monolayer dynamics that explain endocytic reawakening of locomotion in terms of a combination of large-scale directed migration and local unjamming. These changes in multicellular dynamics enable collectives to migrate under physical constraints and may be exploited by tumors for interstitial dissemination.

Polyurethane thermogels show sustained delivery of bioactive anti-VEGFs therapeutics to the eye.

In curved environments, geometric constraints can result in cellular competition for space. Quantitative information about cell geometry was extracted to explore how columnar-like cells fit within the curved anterior of the Drosophila embryo. Cell deformations and cell rearrangements enable packing in this highly curved region.

The aim of this study is about tracing filamentary structures in both neuronal and retinal images. It is often crucial to identify single neurons in neuronal networks, or separate vessel tree structures in retinal blood vessel networks, in applications such as drug screening for neurological disorders or computer-aided diagnosis of diabetic retinopathy. Both tasks are challenging as the same bottleneck issue of filament crossovers is commonly encountered, which essentially hinders the ability of existing systems to conduct large-scale drug screening or practical clinical usage. To address the filament crossovers' problem, a two-step graph-theoretical approach is proposed in this paper. The first step focuses on segmenting filamentary pixels out of the background. This produces a filament segmentation map used as input for the second step, where they are further separated into disjointed filaments. Key to our approach is the idea that the problem can be reformulated as label propagation over directed graphs, such that the graph is to be partitioned into disjoint sub-graphs, or equivalently, each of the neurons (vessel trees) is separated from the rest of the neuronal (vessel) network. This enables us to make the interesting connection between the tracing problem and the digraph matrix-forest theorem in algebraic graph theory for the first time. Empirical experiments on neuronal and retinal image datasets demonstrate the superior performance of our approach over existing methods.

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Summary Recent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month. The present study placed hRPESC-RPE monolayers under the macula of a non-human primate model for 3 months. The transplant was able to recover in vivo and maintained healthy photoreceptors. Importantly, there was no evidence that subretinally transplanted monolayers underwent an epithelial-mesenchymal transition. Neither gliosis in adjacent retina nor epiretinal membranes were observed. These findings suggest that hRPESC-RPE monolayers are safe and may be a useful source for RPE cell replacement therapy.

Understanding the mechanisms of collective cell migration is crucial for cancer metastasis, wound healing and many developmental processes. Imaging a migrating cluster in vivo is feasible, but the quantification of individual cell behaviours remains challenging. We have developed an image analysis toolkit, CCMToolKit, to quantify the Drosophila border cell system. In addition to chaotic motion, previous studies reported that the migrating cells are able to migrate in a highly coordinated pattern. We quantify the rotating and running migration modes in 3D while also observing a range of intermediate behaviours. Running mode is driven by cluster external protrusions. Rotating mode is associated with cluster internal cell extensions that could not be easily characterized. Although the cluster moves slower while rotating, individual cells retain their mobility and are in fact slightly more active than in running mode. We also show that individual cells may exchange positions during migration.

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