Entangled architecture of rough endoplasmic reticulum (RER) and vacuoles enables topological damping in cytoplasm of an ultra-fast giant cell

Cellular systems are known to exhibit some of the fastest movements in the biological world - but little is known as to how single cells can dissipate this energy rapidly and adapt to such large accelerations without sub-cellular damage. To study intracellular adaptations under extreme forces - we investigate Spirostomum ambiguum - a giant cell (1-4mm in length) well known to exhibit ultrafast contractions (50% of body length) within 5 msec with a peak acceleration of 15g. Utilizing transmitted electron microscopy (TEM) and confocal imaging, we discover a novel association of rough endoplasmic reticulum (RER) and vacuoles throughout the cell - forming a contiguous fenestrated cubic membrane architecture that topologically entangles these two organelles. A nearly uniform inter-organelle spacing of 60nm is observed between RER and vacuoles, closely packing the entire cell. Using an overdamped molecular dynamics simulation, we demonstrate how this unique entangled metamaterial responds to external loads by rapidly dissipating energy and helps preserve spatial relationships between organelles. Because this dynamics arises primarily from entanglement of two networks incurring jamming transition at a subcritical volume fraction - we term this phenomena "topological damping". Our findings suggest a new mechanical role of RER-vacuolar meshwork as a metamaterial capable of dissipating energy in an ultra-fast contraction event.

Hepatic and Extrahepatic Sources and Manifestations in Endoplasmic Reticulum Storage Diseases

Alpha-1-antitrypsin (AAT) and fibrinogen are secretory acute phase reactant proteins. Circulating AAT and fibrinogen are synthesized exclusively in the liver. Mutations in the encoding genes result in conformational abnormalities of the two molecules that aggregate within the rough endoplasmic reticulum (RER) instead of being regularly exported. That results in AAT-deficiency (AATD) and in hereditary hypofibrinogenemia with hepatic storage (HHHS). The association of plasma deficiency and liver storage identifies a new group of pathologies: endoplasmic reticulum storage disease (ERSD).

Membranous Structures Directly Come in Contact With p62/SQSTM1 Bodies

During autophagy, autophagosomes are formed to engulf cytoplasmic contents. p62/SQSTM-1 is an autophagic adaptor protein that forms p62 bodies. A unique feature of p62 bodies is that they seem to directly associate with membranous structures. We first investigated the co-localization of mKate2-p62 bodies with phospholipids using click chemistry with propargyl-choline. Propargyl-choline-labeled phospholipids were detected inside the mKate2-p62 bodies, suggesting that phospholipids were present inside the bodies. To clarify whether or not p62 bodies come in contact with membranous structures directly, we investigated the ultrastructures of p62 bodies using in-resin correlative light and electron microscopy of the Epon-embedded cells expressing mKate2-p62. Fluorescent-positive p62 bodies were detected as uniformly lightly osmificated structures by electron microscopy. Membranous structures were detected on and inside the p62 bodies. In addition, multimembranous structures with rough endoplasmic reticulum–like structures that resembled autophagosomes directly came in contact with amorphous-shaped p62 bodies. These results suggested that p62 bodies are unique structures that can come in contact with membranous structures directly:

Pathomorphological changes in the larvae cells of blood-suckıng mosquitoes (Aedes caspius Pallas, 1771) affected by parasitizing microsporidium Amblyospora (=Thelohania) opacita Kudo, 1922

Microsporidia are highly specialized obligate intracellular parasites. They affect various tissues of most animal groups. In Azerbaijan, 29 species and forms of microsporidia were recorded. Of these, 10 species (Amblyospora minuta, Pleistophora obesa, Thelohania opacita, Th. opacita caspius, Th. vexans, Stempellia captshagaica, St. magna, Nosema caspius, Nosema sp., Culicosporella sp.) were found in four species of blood-sucking mosquitos (Culix pipiens pipiens, Aedes vexans, A. caspius, Culex theileri). The collected larvae were identified using the key of Gutsevich et al. (1970). In the laboratory, the mosquito larvae were examined against a dark background under the microscope MBS-9 to distinguish individuals infected with microsporidia. Smears were stained with azure-eosin. Histological slices were prepared according to the Volkova and Yeletskiy method (1971); pathological changes in host tissues were identified using the electron microscope JEM 1400. In the course of our research conducted in 2017–2018 on the Absheron peninsula (Azerbaijan), the life stages of the microsporidium Amblyospora (=Thelohania) opacita Kudo, 1922 were found in the larvae of Aedes caspius Pallas, 1771. Examination of the infected host cell ultrastructure revealed the following changes: rough endoplasmic reticulum and mitochondria concentration around the parasite, an increase of cytoplasm volume, initiation of cell hypertrophy, disappearance of fat, protein granules and rough endoplasmic reticulum at later development stages, a decrease in the number of ribosomes in the cytoplasm and their simultaneous increase around the periphery of the nucleus, mitochondria degradation. These changes cause a delay in the larva development. Microsporidiosis affects the whole mosquito life cycle. The effect of microsporidia on the host organism manifests itself in the delayed larvae development and, in some cases, their early death. First of all, the lipid granules disappear supposedly because of the intensification of the host's aerobic metabolism to compensate for the energy loss caused by the developing parasites.