Effects of local pH on the formation and regulation of cristae morphologies.

Cristae, folded subcompartments of the inner mitochondrial membrane (IMM), have complex and dynamic morphologies. Since cristae are the major site of adenosine triphosphate synthesis, morphological changes of cristae have been studied in relation to functional states of mitochondria. In this sense, investigating the functional and structural significance of cristae may be critical for understanding progressive mitochondrial dysfunction.

Biophysical significance of the inner mitochondrial membrane structure on the electrochemical potential of mitochondria.

The available literature supports the hypothesis that the morphology of the inner mitochondrial membrane is regulated by different energy states, that the three-dimensional morphology of cristae is dynamic, and that both are related to biochemical function. Examination of the correlation between the inner mitochondrial membrane (IMM) structure and mitochondrial energetic function is critical to an understanding of the links between mesoscale morphology and function in progressive mitochondrial dysfunction such as aging, neurodegeneration, and disease. To investigate this relationship, we develop a model to examine the effects of three-dimensional IMM morphology on the electrochemical potential of mitochondria.

Mobile trap algorithm for zinc detection using protein sensors.

We present a mobile trap algorithm to sense zinc ions using protein-based sensors such as carbonic anhydrase (CA). Zinc is an essential biometal required for mammalian cellular functions although its intracellular concentration is reported to be very low. Protein-based sensors like CA molecules are employed to sense rare species like zinc ions.

Assessment of sperm chemokinesis with exposure to jelly coats of sea urchin eggs and resact: a microfluidic experiment and numerical study.

Specific peptides contained within the extracellular layer, or jelly coat, of a sea urchin egg have been hypothesized to play an important role in fertilization, though separate accounting of the effects of chemoattraction, chemokinesis, sperm agglomeration and the other possible roles of the jelly coat have not been reported. In the present study, we used a microfluidic device that allowed determination of the differences in the diffusion coefficients of sperm of the purple sea urchin Arbacia punctulata subjected to two chemoattractants, namely the jelly coat and resact. Our objectives were twofold: (1) to experimentally determine and compare the diffusion coefficients of Arbacia punctulata spermatozoa in seawater, jelly coat solution and resact solution; and (2) to determine the effect of sea urchin sperm diffusion coefficient and egg size on the sperm-egg collision frequency using stochastic simulations.

Receptor for advanced glycation end products activation injures primary sensory neurons via oxidative stress.

The receptor for advanced glycation end products (RAGE) may promote diabetic vascular and renal disease through the activation of intracellular signaling pathways that promote oxidative stress. Oxidative stress is a mediator of hyperglycemia-induced cell injury and a unifying theme for all mechanisms of diabetic complications, but there are few studies on the expression and potential contribution of RAGE in diabetic neuropathy. The current study demonstrates that dorsal root ganglia neurons express functional RAGE and respond to the RAGE ligand S100 with similar downstream signaling, oxidative stress, and cellular injury as other diabetic complication-prone tissues.

Equal and local-load-sharing micromechanical models for collagens: quantitative comparisons in response of non-diabetic and diabetic rat tissue.

Chemical crosslinks in collagens resulting from binding of advanced glycation end-products, have long been presumed to alter the stiffness and permeability of glycated tissues. Recently, we developed a stochastic mechanical model for the response and failure of uniaxially deformed sciatic nerve tissue from diabetic and control rats. Here, we use our model to determine the likely correlation of fibril glycation with failure response, by quantifying statistical differences in their response.

Mitochondria in DRG neurons undergo hyperglycemic mediated injury through Bim, Bax and the fission protein Drp1.

Dorsal root ganglia (DRG) neurons degenerate in diabetic neuropathy (DN) and exhibit mitochondrial damage. We studied mitochondria of cultured DRG neurons exposed to high glucose as an in vitro model of DN. High glucose sequentially increases the expression, activation and localization of the pro-apoptotic proteins Bim and Bax and the mitochondrial fission protein dynamin-regulated protein 1 (Drp1).

Connectivity, clusters, and transport: use of percolation concepts and atomistic simulation to track intracellular ion migration.

The cytoskeleton is an intracellular highway system, teaming with signalling ions that zip from site to site along filaments. These tiny particles alternately embrace and slip free of protein receptors with wide-ranging affinities, as they propagate in a blur of motion along cytoskeletal corridors at transport rates far exceeding ordinary diffusive motion. Recent experimental breakthroughs have enabled optical tracking of these single ion-binding events in the physiological and diseased states.

In situ imaging of mitochondrial outer-membrane pores using atomic force microscopy.

Here we describe a technique for imaging of the outer contours of the mitochondrial membrane using atomic force microscopy, subsequent to or during a toxic or metabolic challenge. Pore formation in both glucose-challenged and 1,3-dinitrobenzene (DNB)-challenged mitochondria was observed using this technique. Our approach enables quantification of individual mitochondrial membrane pore formations.