The effect of hyperglycaemic and hyperlipidemic conditions on cardiac cells in vitro

A simple cell culture model has captured biomechanical effects similar to those observed in myocardial tissue during the onset of diabetic cardiomyopathy.   Cardiac myocytes were co-cultured with cardiac fibroblasts in bilayers mimicking the layered structure of the heart and then exposed to hyperglycaemic or hyperlipidemic conditions associated with diabetes.  In both cases, particle-tracking microrheology revealed myocyte (but not fibroblast) stiffening; AFM measurements supported the microrheological data.  Excess fatty acid also led to increased cFOS expression – and indicator of hypertrophy.   Further experiments hinted at a possible mediating role for reactive oxygen species but more work is required to understand the complex mechanisms underlying the observations.

Hyperglycemic and Hyperlipidemic Conditions Alter Cardiac Cell

Biomechanical Properties; J. Michaelson et al; Biophysical Journal; Volume 106 June 2014 2322–2329

http://www.cell.com/biophysj/abstract/S0006-3495(14)00458-5

Minimally-invasive device with multipoint optical stimulation for optogenetics

Researchers have designed a minimally-invasive device that can selectively and dynamically illuminate multiple brain regions for optogenetics applications.  The device is a waveguide comprising a single thin optical fibre with a sharp, tapered tip coated with gold (except for the tip).  Emission of desired modes of light was permitted at specific sites along the taper by locally removing the coating to create windows.  Each window could be addressed by adjusting the angle of the incident light on the input facet of the fibre.  In vivo proof of principle experiments demonstrated the effectiveness of the device.

Multipoint-Emitting Optical Fibers for Spatially Addressable In Vivo Optogenetics; F. Pisanello et al, Neuron; http://dx.doi.org/10.1016/j.neuron.2014.04.041

http://www.cell.com/neuron/abstract/S0896-6273(14)00356-0

Enhancing combined chemo- and radiotherapy in vivo with nanotechnology

A new targeted cancer therapy termed quadrapeutics (after the four components of the therapy) radically accelerated and improved the effect of combined chemotherapy and radiation in vivo.  Cancer cells self-assembled systemically administered antibody-functionalized gold nanoparticles and drug-loaded nanocarriers into intracellular nanoclusters via receptor-mediated endocytosis.  Near-infra-red laser pulses heated the gold nanoparticles generating vapour plasmonic nanobubbles which then exploded, releasing the drugs from the nanocarriers into the cytoplasm.  Subsequently, xray pulses were locally amplified in the cancer cells through the emission of secondary electrons by the gold nanoparticles in the nanoclusters.  Nanocluster size and thus effectiveness increased with the cancer aggressiveness. 

On-demand intracellular amplification of chemoradiation with cancer-specific plasmonic nanobubbles; Ekaterina Y Lukianova-Hleb et al; Nature Medicine; doi:10.1038/nm.3484

http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3484.html 

Intracellular dynamics probed with nanotubes

The movement of nanotube-labelled kinesin-1 motor proteins in cells was analysed using fluorescence microscopy.  At timeframes above 100 ms, researchers observed a regime of kinesin molecular motion different from thermal motion or directed motor activity.  In this regime, the kinesins were bound to the microtubule network, and moved randomly but remained locally constrained.  Their dynamics reflected nonequilibrium fluctuations in the microtubule network.  These fluctuations were driven by cytoplasmic myosin activity generating a random stirring effect. 

High-resolution mapping of intracellular fluctuations using carbon nanotubes; N. Fakhri et al; Science; Vol 344(6187); p 1031 

http://www.sciencemag.org/content/344/6187/1031.abstract

Mechanics in Biology and Medicine

Researchers from eleven different institutions have identified specific areas of biology and medicine in which mechanics could make significant contributions in a new Perspective article.  Three areas were analysed: nanoparticle-based drug delivery, medical devices, and cell mechanics.

Nanoparticle –based drug delivery is one area ripe with opportunitiy.  In particular, modelling of the drug delivery process would reduce the need for physical experiments and expedite nanoparticle design for improved delivery.  Integrating computational modelling into the rational design of nanoparticles offers the opportunity to improve nanoparticle performance during, for example, vascular transport and endocytosis. 

Modeling also has a role to play in improving a variety of medical devices.  For example, recent developments in “organ-on-chip” devices require understanding of complex transport behaviours through channels, gels and complex tissues.  In another area, advances in ventricular assist devices could greatly benefit from computational mechanics simulations to optimise design and hopefully mitigate problems such as thrombus formation. 

Finally, in the section entitled “cell mechanics”, the authors identified a critical need for better constitutive models for single-cell mechanical behaviour, taking into account the active behaviour of cells.  The mechanics community could also contribute to the development of integrated tools for single cell studies exploring biological variability.

This is just a brief summary of issues that particularly resonated with me.  If you’re interested in the topic, I recommend you go to the full article. This is a long paper, and so my “Bites” length rules are waived for this one.  

USNCTAM perspectives on mechanics in medicine; G. Bao et al, J. R. Soc. Interface 2014 11, 20140301

http://rsif.royalsocietypublishing.org/content/11/97/20140301.abstract

Symmetric protein nanomaterials from novel co-assembling protein subunits

A run of protein-based materials papers (excluding yesterday’s dialysis paper).  Apologies for this – I do try to be diverse in content.  But this one is from my own journal Nature so I couldn’t resist.  Here it is.

Researchers have described the precise self-assembly of protein nanomaterials from two novel co-assembling protein subunits.  Computational methods were used to predict amino acid sequences (one for each subunit) which would stabilize the interfaces between the folded subunits and drive assembly of multiple copies into a specific symmetric architecture.  The researchers experimentally verified the computational methods by fabricating five different two-component co-asssembled nanomaterials each forming one of two targeted tetrahedral architectures.

Accurate design of co-assembling multi-component protein nanomaterials; N.P. King et al; Nature AOP; doi:10.1038/nature13404

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13404.html

A miniaturised kidney dialysis machine for newborn babies

A miniaturised kidney dialysis machine with fluid control capability for newborn babies has been developed.  The dialyzer operates with a much lower volume of blood and very low blood and ultrafiltration flows.  The device allows the use of a small catheter preventing damage to a baby’s blood vessels.  It has been successfully tested on a critically ill newborn baby.  The patient was discharged from intensive care after 39 days.

Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM); C. Ronco et al, The Lancet, Volume 383, Issue 9931, Pages 1807 - 1813, 24th May 2014

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60799-6/fulltext

P.S. learn more about this technology and enjoy a "Cappucino with Claudio Ronco", the lead author of the paper in The Lancet, on Youtube http://www.youtube.com/playlist?list=PL78_fieyQp35MHZ87bD0FnL1pvw7lvweU

A shear stress threshold for angiogenesis

In vitro experiments using microfabricated microfluidic devices have revealed a threshold of shear stress from fluid flow above which endothelial cell monolayers sprout new blood vessels.  The shear stress also sustained the sprout and prevented vessel retraction.  Further experiments revealed that matrix metalloproteinase 1 expression increased dramatically at the shear threshold.  These findings offer a basic mechanism for regulating vessel densities in tissue modulated by other mechanical, geometric,and biochemical factors.

Fluid shear stress threshold regulates angiogenic sprouting; P.A.Galie et al; PNAS; doi:10.1073/pnas.1310842111

http://www.pnas.org/content/early/2014/05/16/1310842111.abstract

Self-powered sensor for human-machine interfacing

Researchers have created a thin-film triboelectric sensor which uses a polymer-nanowire-decorated triboelectric-negative polymer surface to achieve ultrasensitive tactile sensing. The device harnessed the triboelectric charges generated in the polymer surface upon contact with a foreign object to generate an output voltage.  The sensor retained its functionality even when applied to a curved surface.  Demonstrated applications included various alarm systems powered by touch alone.  Approach also offers possibilities for electronic-skin-type technologies. 

Self-Powered, Ultrasensitive, Flexible Tactile Sensors Based on Contact Electrification; G. Zhu et al, Nano Letters; dx.doi.org/10.1021/nl5005652

http://pubs.acs.org/doi/abs/10.1021/nl5005652 

Manipulating cells on magnetic circuit boards

A circuit board of magnetic pathways has enable precise manipulation of magnetic particles and magnetic-nanoparticle-labeled cells in fluidic environments upon application of a rotating magnetic field.  The trajectory of particles was programmable with conducting lines integrated into the circuit board which allowed transportation of particles from one pathway to another. The device had a multiplexed design to facilitate massively parallel single cell operations such as cell sorting, experimentation and retrieval. 

Magnetophoretic circuits for digital control of single particles and cells; B. Lim et al, Nature Communications; DOI: 10.1038/ncomms4846

http://www.nature.com/ncomms/2014/140514/ncomms4846/full/ncomms4846.html

Enhancing photodynamic therapy using biomolecules

Researchers have demonstrated that the upconversion of near-infra-red laser light to visible or ultra-violet by interactions with biomolecules in-situ makes photodynamic therapy more effective.  A known photosensitizer was activated by both near-infra-red light and the upconverted radiation generated by nonlinear optical processes operating in either lipid molecules or collagen.  The approach substantially increased the efficiency with which the photosensitizer destroyed cells in vitro compared to two-photon absorption by near-infra-red alone. 

Photodynamic therapy by in situ nonlinear photon conversion, A. V. Kachynski et al, Nature Photonics AOP, DOI: 10.1038/NPHOTON.2014.90

http://www.nature.com/nphoton/journal/vaop/ncurrent/abs/nphoton.2014.90.html 

Delivering siRNAs to endothelial cells

Scientists have synthesised nanoparticles which efficiently delivered siRNAs to endothelial cells in vivo and facilitated silencing of up to five different endothelial genes concurrently.  Gene expression in several other cell types was not significantly affected by the presence of the delivery agent.  The nanoparticles, made of low-molecular-weight polyamines and lipids, reduced target gene expression in multiple animal models.  In lung cancer models, primary tumour growth and metastases were both reduced. 

In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight; J.E. Dahlman et al, Nature Nanotechnology, DOI: 10.1038/NNANO.2014.84.

http://www.nature.com/nnano/journal/vaop/ncurrent/abs/nnano.2014.84.html

Mechanics of lipid membranes

Researchers describe a method for investigating the viscosity of lipid membranes.  Tracers consisting of two microspheres coupled to a specific lipid allowed measurements of translational and rotational diffusion co-efficient and thus viscosity.  The method showed that adding vesicle trafficking protein Sar1p to membranes resulted in dramatic increase in membrane viscosity.

Measuring Lipid Membrane Viscosity Using Rotational and Translational Probe Diffusion; T.T. Hormel et al; Physical Review Letters; 112, 188101 (2014)

https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.112.188101

Vascularised hydrogels

Researchers have created networks of microchannels in a variety of hydrogels using a micromolding strategy.   Networks of channels enhanced osteogenic cell viability and differentiation in cell-laden micromolded gels.  The channels could be lined with a confluent layer of endothelial cells to create an engineered vasculature.  The hydrogels remained fully perfused. 

Hydrogel Bioprinted Microchannel Networks for Vascularization of Tissue Engineering Constructs; L.E.Bertassoni et al, Lab on a Chip, DOI: 10.1039/C4LC00030G

http://pubs.rsc.org/en/content/articlelanding/2014/lc/c4lc00030g#!divAbstract

Non-invasive monitoring of fetal development

Researchers probed the temporal dynamics of gene transcription in the cell-free RNA of pregnant women’s blood plasma.  Microarray techniques and next-generation sequencing data identified and quantified transcripts from specific fetal tissues and placenta.  Findings suggest a route to diagnosing pregnancy complications and fetal abnormalities.  Methods might also identify neurodegenerative disorders.

Noninvasive in vivo monitoring of tissue-specific global gene expression in humans; W. Koh et al; PNAS; doi: 10.1073/pnas.1405528111

http://www.pnas.org/content/early/2014/05/02/1405528111.abstract

Bone marrow on a chip

Bone marrow grown within a device implanted in a mouse resembles natural marrow, researchers reported.  The tissue could be explanted whole, inserted into a lab-on-a-chip and maintained in vitro for 7 days.  The cultured marrow mimicked tissue responses to radiation toxicity and treatment for exposure normally only observed in vivo.

Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro; Y-S Torisawa et al; Nature Methods AOP doi:10.1038/nmeth.2938

http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.2938.html

Mechanically functional engineered cartilage

Researchers have mimicked mesenchymal condensation using a cellular self-assembly method to successfully generate centimetre-sized anatomically-shaped cartilage from human mesenchymal stem cells.  The engineered tissue was stratified with physiologically relevant values of Young’s modulus and co-efficient of friction.  In vitro data suggested the method could be used to repair cartilage defects.

Large, stratified and mechanically functional human cartilage grown in vitro by mesenchymal condensation, S. Bhumiritana et al, PNAS, doi/10.1073/pnas.1324050111

http://www.pnas.org/content/early/2014/04/25/1324050111.full

Simulating neural networks

A fast and energy efficient circuit board which models neural circuits in the human brain offers new opportunities for robotics and brain-machine interfaces.  The device contains 16 chips and consumes just three watts to simulate in real time the computing capability of a million neurons with billions of synaptic connections.

http://ieeexplore.ieee.org/xpl/articleDetails.jsp?arnumber=6805187

Neurogrid: A mixed-analog-digital multichip system for large-scale neural simulations; B.V.Benjamin et al; Proceedings of the IEEE; DOI 10.1109/JPROC.2014.2313565; 2014.

Lab-on-a-chip based blood plasma separation

Researchers have developed a cheap microfluidic device to separate plasma from whole blood with efficiency similar to centrifugation.  A filter at the top of a channel with blood flowing upwards separated the fluid phase from the cells. Gravity-assisted sedimentation prevented cells clogging the filter and subsequent hemolysis.

Hemolysis-free blood plasma separation, JH Son et al, Lab-on-a-chip, 2014, Accepted Manuscript, DOI: 10.1039/C4LC00149D

Link to article:

http://pubs.rsc.org/en/Content/ArticleLanding/2014/LC/C4LC00149D?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FLC+(RSC+-+Lab+Chip+latest+articles)#!divAbstract

Mechanism of cell migration in confined channels

Cells may experience physical confinement when migrating through extracellular matrices.  In confinement, processes typically associated with 2D migration e.g. actin polymerization are inhibited.  Now, a chemotaxis-based microfluidic device containing microchannels of varying cross-sectional areas reveals an alternative mechanism of migration in confinement: water permeation and active and passive ion transport.

http://www.cell.com/cell/abstract/S0092-8674(14)00340-7

Water Permeation Drives Tumor Cell Migration in Confined Microenvironments; K.M. Stroka et al, Cell 157, 611–623, April 24, 2014