Transmission Of Information In Cells Research Articles

The Role of Mitophagy in Ischemic Stroke.

Mitochondria are important places for eukaryotes to carry out energy metabolism and participate in the processes of cell differentiation, cell information transmission, and cell apoptosis. Autophagy is a programmed intracellular degradation process. Mitophagy, as a selective autophagy, is an evolutionarily conserved cellular process to eliminate dysfunctional or redundant mitochondria, thereby fine-tuning the number of mitochondria and maintaining energy metabolism. Many stimuli could activate mitophagy to regulate related physiological processes, which could ultimately reduce or aggravate the damage caused by stimulation. Stroke is a common disease that seriously affects the health and lives of people around the world, and ischemic stroke, which is caused by cerebral vascular stenosis or obstruction, accounts for the vast majority of stroke. Abnormal mitophagy is closely related to the occurrence, development and pathological mechanism of ischemic stroke. However, the exact mechanism of mitophagy involved in ischemic stroke has not been fully elucidated. In this review, we discuss the process and signal pathways of mitophagy, the potential role of mitophagy in ischemic stroke and the possible signal transduction pathways. It will help deepen the understanding of mitophagy and provide new ideas for the treatment of ischemic stroke.

Direct investigation of charge transfer in neurons by electrostatic force microscopy

Charge transfer plays fundamental roles in information transmission in cells, especially in neurons. To date, direct observation of charge propagation in neurons at nanometer level has not been achieved yet. Herein, a combined charge injection and Electrostatic Force Microscopy (EFM) detection approach is applied to directly study charge propagation and distribution at nanometer resolution in spines and synapses of hippocampal neurons. Charge density, charge mobility and membrane potential in neural signal transmission process through the spines of axons and dendrites of hippocampal neurons were investigated quantitatively. Postsynaptic densities (PSD) in spines of axons and dendrites were revealed and studied. The methods and results from present work provide insights into physiological activities and processes related with electrical properties in nervous system and other biological samples.

Fluctuations, Correlations and the Estimation of Concentrations inside Cells.

Information transmission in cells occurs quite accurately even when concentration changes are “read” by individual binding sites. In this paper we study ligand number and site occupancy fluctuations when ligands diffuse and react going beyond the analyses that focus on their asymptotic decay. In this way we show that, for immobile binding sites, fluctuations in the number of bound molecules decay on a relatively fast scale before the asymptotic behavior kicks in. This result can explain the observed co-existence of highly fluctuating instantaneous transcriptional activities with accumulated mRNA concentrations that have relatively small noise levels. We also show that the initial stages of the decay in the bound molecule number fluctuations have one or two characteristic timescales depending on the concentration of free molecules. This transition can explain the changes in enzyme activity observed at the single molecule level.

Spatial Control of Biochemical Modification Cascades and Pathways

Information transmission in cells occurs through complex networks of proteins and genes and is relayed through cascades of biochemical modifications, which are typically studied through ordinary differential equations. However, it is becoming increasingly clear that spatial factors can strongly influence chemical information transmission in cells. In this article, we systematically disentangle the effects of space in signaling cascades. This is done by examining the effects of localization/compartmentalization and diffusion of enzymes and substrates in multiple variants of chemical modification cascades. This includes situations where the modified form of species at one stage 1) acts as an enzyme for the next stage; 2) acts as a substrate for the next stage; and 3) is involved in phosphotransfer. Our analysis reveals the multiple effects of space in signal transduction cascades. Although in some cases space plays a modulatory effect (itself of interest), in other cases, spatial regulation and control can profoundly affect the nature of information processing as a result of the subtle interplay between the patterns of localization of species, diffusion, and the nature of the modification cascades. Our results provide a platform for disentangling the role of space and spatial control in multiple cellular contexts and a basis for engineering spatial control in signaling cascades through localization/compartmentalization.

Concentration Estimates from Counting Individual Molecules

The transmission of information in cells usually involves changes in concentration that need to be read by different cell components. Very often small molecule numbers are involved so that fluctuations play a relevant role. In this work we study molecule number fluctuations when molecules diffuse and react. Building upon our previous works on the analysis of Fluorescence Correlation Spectroscopy experiments we derive a formula for the observation time that is needed to estimate concentrations with a given precision out of counting individual molecules. In this way we determine that fluctuations in the number of bound molecules can be averaged out on a relatively fast timescale due to correlations and that they are described by either one or two characteristic timescales depending on the concentration of free molecules. We show that how our results can be used to understand the transformation from a highly fluctuating instantaneous transcriptional activity into the expected output concentration relatively fast and to analyze the dynamics of enzymes at the single molecule level.

Bi-stability, hysteresis, and memory of voltage-gated lysenin channels

Lysenin, a 297 amino acid pore-forming protein extracted from the coelomic fluid of the earthworm E. foetida, inserts constitutively open large conductance channels in natural and artificial lipid membranes containing sphingomyelin. The inserted channels show voltage regulation and slowly close at positive applied voltages. We report on the consequences of slow voltage-induced gating of lysenin channels inserted into a planar Bilayer Lipid Membrane (BLM), and demonstrate that these pore-forming proteins constitute memory elements that manifest gating bi-stability in response to variable external voltages. The hysteresis in macroscopic currents dynamically changes when the time scale of the voltage variation is smaller or comparable to the characteristic conformational equilibration time, and unexpectedly persists for extremely slow-changing external voltage stimuli. The assay performed on a single lysenin channel reveals that hysteresis is a fundamental feature of the individual channel unit and an intrinsic component of the gating mechanism. The investigation conducted at different temperatures reveals a thermally stable reopening process, suggesting that major changes in the energy landscape and kinetics diagram accompany the conformational transitions of the channels. Our work offers new insights on the dynamics of pore-forming proteins and provides an understanding of how channel proteins may form an immediate record of the molecular history which then determines their future response to various stimuli. Such new functionalities may uncover a link between molecular events and macroscopic processing and transmission of information in cells, and may lead to applications such as high density biologically-compatible memories and learning networks.