3D Cellular Membrane Systems Highlighted on BiophysJ Cover

bpj_104_11_coverMasa Hoshijima and Christian Soeller, authors on the latest paper to be highlighted on the cover of the Biophysical Journal, detail the process of creating the image below. The paper, Nanoscale distribution of ryanodine receptors and caveolin-3 in mouse ventricular myocytes: dilation of t-tubules near junctions, was co-authored by Joseph Wong, David Baddeley, Eric A. Bushong, Zeyun Yu, Mark H. Ellisman, Hoshijima, and Soeller.

The cover image shows a 3D snapshot of cellular membrane systems that are essential to the rapid electrical activation of cardiac muscle cells. We acquired hundreds of serial high-resolution scanning electron microscopy (SEM) images from a heart tissue-embedded plastic block, determined membrane profiles, and created the rendering of the transverse tubular system (green), which is a complex network of membrane invaginations continuous with the surface membrane (blue-black). We are also showing junctional contacts (red) between the transverse tubular system with the sarcoplasmic reticulum, an internal membrane-bound compartment that is an intracellular reservoir of calcium, which acts as a chemical activator of the contractile proteins. The signaling between these two membrane systems occurs at the junctional contacts, where they come to within ~15 nm of each other.

The serial imaging method is termed serial block-face SEM, one of the newer volume electron microscopic technologies, which are gaining in popularity. In this method, the surface of tissue blocks is sectioned in situ in specially designed SEM vacuum chambers. The original interest, which drove the development of volume electron microscopy methods, was largely in the visualization of neuronal circuits. However, the method is generally useful to visualize a whole cell or a large fraction of a whole cell, with extremely fine details of their structural complexity. We were struck by the dramatic and beautiful features of the rendered structures and thought it would make a suitable cover of Biophysical Journal.

The nanoscale detail of the membrane network architecture is biophysically very important as it determines propagation of electrical signals, diffusion of signaling and messenger compounds (such as calcium) and – via junctional contacts – strongly affects signaling between channels in the surface membrane and the sarcoplasmic reticulum. All of these interactions are critical for the forceful and rapid contraction of heart muscle. Our manuscript reveals details and structural specializations of the transverse tubular system that were not shown before in such clarity and identified local swellings of the tubules that often occurred at junctions with the sarcoplasmic reticulum.

Our accompanying publication was the result of a collaboration between the University of Auckland (now University of Exeter, Soeller) and University of California San Diego (UCSD) (Hoshijima) using a range of imaging techniques: (1) the SEM imaging highlighted on the cover, (2) EM tomography for the highest resolution in small volumes and (3) optical super-resolution imaging which we used for quantification and protein specific imaging of key molecules associated with these membranes. We believe our paper demonstrates the power of correlative imaging between modern EM techniques and optical super-resolution with fluorescent markers. We are continuing to pursue this theme in a new collaboration between our laboratories in San Diego (Hoshijima), Exeter (Soeller), and in addition colleagues in Kyoto (Dr. Hiroshi Takeshima), supported by a recently funded Human Frontier Science Program research project to reveal the makeup and assembly of nano-signaling structures.

Imaging is the key technology in both of our laboratories and as a result our work is generally very visual. In addition to the scientific information the images often have a great aesthetic appeal to us. The fact that one of our images has been chosen as cover art of the current issue of biophysical journal is greatly encouraging since it means that others can see the aesthetic value, too. Most important to us, however, is the scientific value of our images – they contain important information and we see it as one of our key tasks to reduce the data in our images to biophysical quantities that can be related to hypotheses and quantitative models. This brings us to perhaps the most significant reason we are very happy that our art is on the cover of the Biophysical Journal: it implies that one of our manuscripts has been accepted and that our image data and the information it conveys has passed the peer review of BJ.

Links to further work of Dr. Soeller’s laboratory and imaging activities are available at http://emps.exeter.ac.uk/physics-astronomy/staff/cs463. To learn more about the active development of various advanced microscopic imaging technologies at UCSD, please visit http://ncmir.ucsd.edu.


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