Microglia mechanics : immune activation alters traction forces and durotaxis

This work was supported by the Austrian Agency for International Cooperation in Education and Research (Scholarship to LB), Faculty of Computer Science and Biomedical Engineering at Graz University of Technology (Scholarship to LB), German National Academic Foundation (Scholarship to DK), Wellcome Trust/University of Cambridge Institutional Strategic Support Fund (Research Grant to KF), Isaac Newton Trust (Research Grant 14.07 (m) to KF), Leverhulme Trust (Research Project Grant RPG-2014-217 to KF), UK Medical Research Council (Career Development Award to KF), and the Human Frontier Science Program (Young Investigator Grant RGY0074/2013 to GS, MG, and KF). Date of Acceptance: 31/08/2015Microglial cells are key players in the primary immune response of the central nervous system. They are highly active and motile cells that chemically and mechanically interact with their environment. While the impact of chemical signaling on microglia function has been studied in much detail, the current understanding of mechanical signaling is very limited. When cultured on compliant substrates, primary microglial cells adapted their spread area, morphology, and actin cytoskeleton to the stiffness of their environment. Traction force microscopy revealed that forces exerted by microglia increase with substrate stiffness until reaching a plateau at a shear modulus of ~5 kPa. When cultured on substrates incorporating stiffness gradients, microglia preferentially migrated toward stiffer regions, a process termed durotaxis. Lipopolysaccharide-induced immune-activation of microglia led to changes in traction forces, increased migration velocities and an amplification of durotaxis. We finally developed a mathematical model connecting traction forces with the durotactic behavior of migrating microglial cells. Our results demonstrate that microglia are susceptible to mechanical signals, which could be important during central nervous system development and pathologies. Stiffness gradients in tissue surrounding neural implants such as electrodes, for example, could mechanically attract microglial cells, thus facilitating foreign body reactions detrimental to electrode functioning.Publisher PDFPeer reviewe

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

Microlaser-based contractility sensing in single cardiomyocytes and whole hearts

Microscopic whispering gallery mode lasers detect minute changes in cellular refractive index inside individual cardiac cells and in live zebrafish. We show that these signals encode cardiac contractility that can be used for intravital sensing.Postprin

Optofluidic distributed feedback lasers with evanescent pumping : reduced threshold and angular dispersion analysis

The authors acknowledge financial support from the European Research Council (ERC StG ABLASE, 640012), the Scottish Funding Council (via SUPA) and the European Union Marie Curie Career Integration Grant (PCIG12-GA-2012-334407). M.K. and G.L.W. acknowledge funding from the EPSRC DTG (EP/M506631/1 and EP/K503162/1). M.S. acknowledges funding from the European Commission for a Marie Sklodowska-Curie Individual Fellowship (659213). I.D.W.S. acknowledges funding from a Royal Society Wolfson research merit award. The research data supporting this publication can be accessed at http://dx.doi.org/10.17630/0ed7dad7-75e1-4ab9-9845-c455d1a7c6a4.We demonstrate an evanescently pumped water-based optofluidic DFB laser with a record low pump threshold of ETH = 520 nJ. The low threshold results from an optimized mode shape, which is achieved by a low refractive index substrate, and from the use of a mixed-order DFB grating. Investigating the photonic band structure via angular dispersion analysis both above and below lasing threshold allows us to measure the refractive index of the liquid gain layer and to determine device parameters such as the waveguide core layer thickness. We show that it is possible to tailor the divergence of the lasing emission by varying the number of second order grating periods used for outcoupling.Publisher PDFPeer reviewe

Advances in small lasers

M.T.H was supported by an Australian Research council Future Fellowship research grant for this work. M.C.G. is grateful to the Scottish Funding Council (via SUPA) for financial support.Small lasers have dimensions or modes sizes close to or smaller than the wavelength of emitted light. In recent years there has been significant progress towards reducing the size and improving the characteristics of these devices. This work has been led primarily by the innovative use of new materials and cavity designs. This Review summarizes some of the latest developments, particularly in metallic and plasmonic lasers, improvements in small dielectric lasers, and the emerging area of small bio-compatible or bio-derived lasers. We examine the different approaches employed to reduce size and how they result in significant differences in the final device, particularly between metal- and dielectric-cavity lasers. We also present potential applications for the various forms of small lasers, and indicate where further developments are required.PostprintPeer reviewe

Photostimulation for in vitro optogenetics with high power blue organic light-emitting diodes

Funding: Leverhulme Trust (RPG-2017-231), the EPSRC NSF-CBET lead agency agreement (EP/R010595/1, 1706207), the DARPA NESD programme (N66001-17-C-4012) and the RS Macdonald Charitable Trust. C.M. acknowledges funding by the European Commission through a Marie Sklodowska-Curie Individual Fellowship (703387). Y. L. Deng acknowledges support from the Chinese Scholarship Council (CSC).Optogenetics, photostimulation of neural tissues rendered sensitive to light, is widely used in neuroscience to modulate the electrical excitability of neurons. For effective optical excitation of neurons, light wavelength and power density must fit with the expression levels and biophysical properties of the genetically encoded light‐sensitive ion channels used to confer light sensitivity on cells—most commonly, channelrhodopsins (ChRs). As light sources, organic light‐emitting diodes (OLEDs) offer attractive properties for miniaturized implantable devices for in vivo optical stimulation, but they do not yet operate routinely at the optical powers required for optogenetics. Here, OLEDs with doped charge transport layers are demonstrated that deliver blue light with good stability over millions of pulses, at powers sufficient to activate the ChR, CheRiff when expressed in cultured primary neurons, allowing live cell imaging of neural activity with the red genetically encoded calcium indicator, jRCaMP1a. Intracellular calcium responses scale with the radiant flux of OLED emission, when varied through changes in the current density, number of pulses, frequency, and pulse width delivered to the devices. The reported optimization and characterization of high‐power OLEDs are foundational for the development of miniaturized OLEDs with thin‐layer encapsulation on bioimplantable devices to allow single‐cell activation in vivo.Publisher PDFPeer reviewe

Coherent Random Lasing Realized in Polymer Vesicles

We have demonstrated the realization of a coherent vesicle random lasing (VRL) from the dye doped azobenzene polymer vesicles self-assembled in the tetrahydrofuran-water system, which contains a double-walled structure: a hydrophilic and hydrophobic part. The effect of the dye and azobenzene polymer concentration on the threshold of random laser has been researched. The threshold of random laser decreases with an increase in the concentration of the pyrromethene 597 (PM597) laser and azobenzene polymer. Moreover, the scattering of small size group vesicles is attributed to providing a loop to boost the coherent random laser through the Fourier transform analysis. Due to the vesicles having the similar structure with the cell, the generation of coherent random lasers from vesicles expand random lasers to the biomedicine filed

Benzofuran-fused Phosphole: Synthesis, Electronic, and Electroluminescence Properties

International audienceA synthetic route to novel benzofuran-fused phosphole derivatives 3-5 is described. These compounds showed optical and electrochemical properties that differ from their benzothiophene analog. Preliminary results show that 4 can be used as an emitter in OLEDs, illustrating the potential of these new compounds for opto-electronic applications