Identifying the cues followed by cells is key to understand processes as embryonic development, tissue homeostasis, or several pathological conditions. Based on a durotaxis model, it is shown that cells moving on predeformed thin elastic membrane follow the direction of increasing strain of the substrate. This mechanism, straintaxis, does not distinguish the origin of the strain, but the active stresses produce large strains on cells or tissues being used as substrates. Hence, straintaxis is the natural realization of duratoaxis in vivo. Considering a circular geometry for the substrate cells, it is shown that if the annular component of the active stress component increases with the radial distance, cells migrate toward the substrate cell borders. With appropriate estimation for the different parameters, the migration speeds are similar to those obtained in recent experiments [Reig et al. Nat. Comm. 2017, 8, 15431]. In these, during the annual killifish epiboly, deep cells that move in contact with the epithelial enveloping cell layer (EVL), migrate toward the EVL cell borders with speeds of microns per minute.

The developmental strategies used by progenitor cells to endure a safe journey from their induction place towards the site of terminal differentiation are still poorly understood. Here we uncovered a progenitor cell allocation mechanism that stems from an incomplete process of epithelial delamination that allows progenitors to coordinate their movement with adjacent extra-embryonic tissues. Progenitors of the zebrafish laterality organ originate from the surface epithelial enveloping layer by an apical constriction process of cell delamination. During this process, progenitors retain long-term apical contacts that enable the epithelial layer to pull a subset of progenitors along their way towards the vegetal pole. The remaining delaminated progenitors follow apically-attached progenitors' movement by a co-attraction mechanism, avoiding sequestration by the adjacent endoderm, ensuring their fate and collective allocation at the differentiation site. Thus, we reveal that incomplete delamination serves as a cellular platform for coordinated tissue movements during development.

The developmental strategies used by progenitor cells to allow a safe journey from their induction place towards the site of terminal differentiation are still poorly understood. Here we uncovered a mechanism of progenitor cell allocation that stems from an incomplete process of epithelial delamination that allows progenitors to coordinate their movement with adjacent extra-embryonic tissues. Progenitors of the zebrafish laterality organ originate from the superficial epithelial enveloping layer by an apical constriction process of cell delamination. During this process, progenitors retain long-lasting apical contacts that enable the epithelial layer to pull a subset of progenitors on their way to the vegetal pole. The remaining delaminated cells follow the movement of apically attached progenitors by a protrusion-dependent cell-cell contact mechanism, avoiding sequestration by the adjacent endoderm, ensuring their collective fate and allocation at the site of differentiation. Thus, we reveal that incomplete delamination serves as a cellular platform for coordinated tissue movements during development.

Basement membrane is composed of ECM proteins that have viscoelastic properties. When the viscoelasticity is mimicked in vitro, epithelial cells coalesce by ''dragging'' the ECM protein through the PDMS substrate. This mechanosensing of viscoelasticity is achieved through the translocation of vinculin from the focal adhesions to the cell-cell junctions and is sensitive to the level of vinculin in the cell. Apart from the composition of cell-matrix and cell-cell adhesion complexes within the cell, we find that other biophysical and biochemical cues from environment affect the cell response on a viscoelastic substrate. By varying the interfacial force between ECM protein, fibronectin, and the PDMS substrate through physisorption or covalent linkage, we found that increasing the adhesion force hinders the coalescence of cells on a viscoelastic substrate as if on a soft-elastic substrate, suggesting the role of ECM-substrate interaction for in vitro models. Also, stronger cell-cell adhesions cause coalescence when coated with either fibronectin or collagen-1 alone but not when coated with Matrigel, consisting of collagen-IV, laminin, and other ECM proteins. To gain further insights into this phenomenon, we are using quantitative super-resolution microscopy to investigate how the difference in ECM anchoring is sensed by the cell at the molecular level and traction force microscopy to quantify the ECM remodeling and substrate deformation. These results on the viscoelastic substrate would provide new insights into in vivo basement membrane and cell-cell dynamics in general, and help to have better in vitro model, mimicking in vivo ECM arrangement and viscoelasticity, where these are crucial. 2711-Pos IPMK Loss Inhibits Cellular Motility and Contractility .Cellular adhesion is dependent on the type of adhesion receptors displayed on the cell surface, and activation of adhesion receptors initiates downstream signaling cascades that are context dependent. Cellular expression of adhesion receptors is modulated by a complex array of extracellular and intracellular signals, and we have found that Inositol Phosphate Multikinase (IPMK) is a transcriptional regulator of integrin b1 protein in murine embryonic fibroblast (MEF) cells. Further, we show that although loss of IPMK dramatically reduces levels of both active and inactive integrin b1 protein, activation of the focal adhesion proteins FAK and Src are increased while total protein levels are unchanged, suggesting that IPMK is a negative regulator of focal adhesion complex activity. Importantly, IPMK regulation of integrin gene expression is activity dependent. Using native extracellular matrix mimicking fibers as substrate, generated using STEP (Spinneret-based Tunable Engineered Parameters) technique, we show that loss of this enzyme inhibits migration (0.68 mm/min in Wild Type cells vs 0.35 mm/min in IPMK Knock-out cells) due to decreased cell-matrix adhesion and reduced cellular contractility. Using nanonet force microscopy (NFM), we calculated the forces of migrating ...

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