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

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

Mechanics of stem cell nuclei

The cross-section of most materials contracts when stretched and expands when compressed. Auxetic materials do the opposite. Researchers now show that embryonic stem cell nuclei become auxetic when they enter a metastable state prior to differentiation. Data suggest that this is driven at least in part by global chromatin decondensation.

http://www.nature.com/nmat/journal/vaop/ncurrent/full/nmat3943.html

Auxetic nuclei in embryonic stem cells exiting pluripotency; S. Pagliara et al; Nature Materials (AOP); doi:10.1038/nmat3943