Laminin levels regulate tissue migration and anterior-posterior polarity during egg morphogenesis in Drosophila

Basement membranes (BMs) are specialized extracellular matrices required for tissue organisation and organ formation. Here we study the role of laminin and its integrin receptor in the regulation of tissue migration during Drosophila oogenesis. In the fly, egg production involves the collective migration of follicle cells (FCs) over the BM to shape the mature egg. We quantify laminin and integrin levels to show that laminin contents in the BM increase with time, while integrin amounts in the FCs do not vary significantly. Controlled manipulation of integrin and laminin levels revealed that a dynamic balance of integrin-laminin amounts determines the onset and speed of FC migration. Thus, the interplay of ligand-receptor levels regulates tissue migration in vivo. In addition, reduced laminin contents affect the ultrastructure and biophysical properties of the BM. Finally, laminin depletion results also in anterior-posterior misorientation of developing follicles. Altogether, laminin emerges as a key new player in the regulation of collective cell migration, tissue stiffness and the organisation of anterior-posterior polarity in Drosophila

Brain tissue mechanics is governed by microscale relations of the tissue constituents

Local mechanical tissue properties are a critical regulator of cell function in the central nervous system (CNS) during development and disorder. However, we still don't fully understand how the mechanical properties of individual tissue constituents, such as cell nuclei or myelin, determine tissue mechanics. Here we developed a model predicting local tissue mechanics, which induces non-affine deformations of the tissue components. Using the mouse hippocampus and cerebellum as model systems, we show that considering individual tissue components alone, as identified by immunohistochemistry, is not sufficient to reproduce the local mechanical properties of CNS tissue. Our results suggest that brain tissue shows a universal response to applied forces that depends not only on the amount and stiffness of the individual tissue constituents but also on the way how they assemble. Our model may unify current incongruences between the mechanics of soft biological tissues and the underlying constituents and facilitate the design of better biomedical materials and engineered tissues. To this end, we provide a freely-available platform to predict local tissue elasticity upon providing immunohistochemistry images and stiffness values for the constituents of the tissue

The Effect of Dissolved Polyunsaturated Aldehydes on Microzooplankton Growth Rates in the Chesapeake Bay and Atlantic Coastal Waters

Allelopathy is wide spread among marine phytoplankton, including diatoms, which can produce cytotoxic secondary metabolites such as polyunsaturated aldehydes (PUA). Most studies on diatom-produced PUA have been dedicated to their inhibitory effects on reproduction and development of marine invertebrates. However, little information exists on their impact on key herbivores in the ocean, microzooplankton. This study examined the effects of dissolved 2E,4E-octadienal and 2E,4E-heptadienal on the growth rates of natural ciliate and dinoflagellate populations in the Chesapeake Bay and the coastal Atlantic waters. The overall effect of PUA on microzooplankton growth was negative, especially at the higher concentrations, but there were pronounced differences in response among common planktonic species. For example, the growth of Codonella sp., Leegaardiella sol, Prorodon sp., and Gyrodinium spirale was impaired at 2 nM, whereas Strombidium conicum, Cyclotrichium gigas, and Gymnodinium sp. were not affected even at 20 nM. These results indicate that PUA can induce changes in microzooplankton dynamics and species composition

Constriction imposed by basement membrane regulates developmental cell migration

The basement membrane (BM) is a specialized extracellular matrix (ECM), which underlies or encases developing tissues. Mechanical properties of encasing BMs have been shown to profoundly influence the shaping of associated tissues. Here, we use the migration of the border cells (BCs) of the Drosophila egg chamber to unravel a new role of encasing BMs in cell migration. BCs move between a group of cells, the nurse cells (NCs), that are enclosed by a monolayer of follicle cells (FCs), which is, in turn, surrounded by a BM, the follicle BM. We show that increasing or reducing the stiffness of the follicle BM, by altering laminins or type IV collagen levels, conversely affects BC migration speed and alters migration mode and dynamics. Follicle BM stiffness also controls pairwise NC and FC cortical tension. We propose that constraints imposed by the follicle BM influence NC and FC cortical tension, which, in turn, regulate BC migration. Encasing BMs emerge as key players in the regulation of collective cell migration during morphogenesis

Mechanosensing is critical for axon growth in the developing brain.

During nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signaling. However, growing neurons interact not only chemically but also mechanically with their environment. Here we identify mechanical signals as important regulators of axon pathfinding. In vitro, substrate stiffness determined growth patterns of Xenopus retinal ganglion cell axons. In vivo atomic force microscopy revealed a noticeable pattern of stiffness gradients in the embryonic brain. Retinal ganglion cell axons grew toward softer tissue, which was reproduced in vitro in the absence of chemical gradients. To test the importance of mechanical signals for axon growth in vivo, we altered brain stiffness, blocked mechanotransduction pharmacologically and knocked down the mechanosensitive ion channel piezo1. All treatments resulted in aberrant axonal growth and pathfinding errors, suggesting that local tissue stiffness, read out by mechanosensitive ion channels, is critically involved in instructing neuronal growth in vivo.This work was supported by the German National Academic Foundation (scholarship to D.E.K.), Wellcome Trust and Cambridge Trusts (scholarships to A.J.T.), Winston Churchill Foundation of the United States (scholarship to S.K.F.), Herchel Smith Foundation (Research Studentship to S.K.F.), CNPq 307333/2013-2 (L.d.F.C.), NAP-PRP-USP and FAPESP 11/50761-2 (L.d.F.C.), UK EPSRC BT grant (J.G.), Wellcome Trust WT085314 and the European Research Council 322817 grants (C.E.H.); an Alexander von Humboldt Foundation Feodor Lynen Fellowship (K.F.), UK BBSRC grant BB/M021394/1 (K.F.), the Human Frontier Science Program Young Investigator Grant RGY0074/2013 (K.F.), the UK Medical Research Council Career Development Award G1100312/1 (K.F.) and the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number R21HD080585 (K.F.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/nn.439

Cortical cell stiffness is independent of substrate mechanics

Cortical stiffness is an important cellular property that changes during migration, adhesion and growth. Previous atomic force microscopy (AFM) indentation measurements of cells cultured on deformable substrates have suggested that cells adapt their stiffness to that of their surroundings. Here we show that the force applied by AFM to a cell results in a significant deformation of the underlying substrate if this substrate is softer than the cell. This ‘soft substrate effect’ leads to an underestimation of a cell’s elastic modulus when analysing data using a standard Hertz model, as confirmed by finite element modelling and AFM measurements of calibrated polyacrylamide beads, microglial cells and fibroblasts. To account for this substrate deformation, we developed a ‘composite cell–substrate model’. Correcting for the substrate indentation revealed that cortical cell stiffness is largely independent of substrate mechanics, which has major implications for our interpretation of many physiological and pathological processes

The role of cell body density in ruminant retina mechanics assessed by atomic force and Brillouin microscopy

Cells in the central nervous system (CNS) respond to the stiffness of their environment. CNS tissue is mechanically highly heterogeneous, thus providing motile cells with region-specific mechanical signals. While CNS mechanics has been measured with a variety of techniques, reported values of tissue stiffness vary greatly, and the morphological structures underlying spatial changes in tissue stiffness remain poorly understood. We here exploited two complementary techniques, contact-based atomic force microscopy and contact-free Brillouin microscopy, to determine the mechanical properties of ruminant retinae, which are built up by different tissue layers. As in all vertebrate retinae, layers of high cell body densities ('nuclear layers') alternate with layers of low cell body densities ('plexiform layers'). Different tissue layers varied significantly in their mechanical properties, with the photoreceptor layer being the stiffest region of the retina, and the inner plexiform layer belonging to the softest regions. As both techniques yielded similar results, our measurements allowed us to calibrate the Brillouin microscopy measurements and convert the Brillouin shift into a quantitative assessment of elastic tissue stiffness with optical resolution. Similar as in the mouse spinal cord and the developing Xenopus brain, we found a strong correlation between nuclear densities and tissue stiffness. Hence, the cellular composition of retinae appears to strongly contribute to local tissue stiffness, and Brillouin microscopy shows a great potential for the application in vivo to measure the mechanical properties of transparent tissues.IPW is a recipient of an EMBO Long-Term Fellowship (ALTF 1263-2015; European Commission FP7 (Marie Curie Actions, LTFCOFUND2013, GA-2013-609409)). This work was further supported by the National Science Foundation (CMMI-1562863 to SHY and CMMI-1537027 to GS), the Human Frontier Science Program Young Investigator Grant RGY0074/2013 (GS and KF), the UK Medical Research Council Career Development Award G1100312/1 (KF), and the National Institutes of Health (R01EY025454 to SHY, K25EB015885 and R33CA204582 to GS, R21HD080585 to KF)

Integration von Telelearning- und Teleworking-Applikationen

Aus der Kurzfassung: 'Ca. 5 % der deutschen Arbeitnehmer gehören zu einer der weltweit am rasantesten wachsenden Berufsgruppen: den Telearbeitern. Rund elf Millionen Amerikaner arbeiten bereits regelmäßig daheim - Tendenz steigend. Europa ist vergleichsweise rückständig, doch soll es in Deutschland bis zur Jahrtausendwende schon 800.000 Teleworker geben. [9] Damit diese Arbeitsform ihr Produktivitätspotential ganz entfaltet, gilt es jedoch, Teleworker ausreichend auf ihr neues Arbeitsumfeld und die neue Technik vorzubereiten

Integration von Telelearning- und Teleworking-Applikationen

Aus der Kurzfassung: 'Ca. 5 % der deutschen Arbeitnehmer gehören zu einer der weltweit am rasantesten wachsenden Berufsgruppen: den Telearbeitern. Rund elf Millionen Amerikaner arbeiten bereits regelmäßig daheim - Tendenz steigend. Europa ist vergleichsweise rückständig, doch soll es in Deutschland bis zur Jahrtausendwende schon 800.000 Teleworker geben. [9] Damit diese Arbeitsform ihr Produktivitätspotential ganz entfaltet, gilt es jedoch, Teleworker ausreichend auf ihr neues Arbeitsumfeld und die neue Technik vorzubereiten

Soft Polydimethylsiloxane-Supported Lipid Bilayers for Studying T Cell Interactions.

Much of what we know about the early stages of T cell activation has been obtained from studies of T cells interacting with glass-supported lipid bilayers that favor imaging but are orders of magnitude stiffer than typical cells. We developed a method for attaching lipid bilayers to polydimethylsiloxane polymer supports, producing "soft bilayers" with physiological levels of mechanical resistance (Young's modulus of 4 kPa). Comparisons of T cell behavior on soft and glass-supported bilayers revealed that whereas late stages of T cell activation are thought to be substrate-stiffness dependent, early calcium signaling was unaffected by substrate rigidity, implying that early steps in T cell receptor triggering are not mechanosensitive. The exclusion of large receptor-type phosphatases was observed on the soft bilayers, however, even though it is yet to be demonstrated at authentic cell-cell contacts. This work sets the stage for an imaging-based exploration of receptor signaling under conditions closely mimicking physiological cell-cell contact.Royal Societ