Biophysical State Research Articles

Age-specific and compartment-dependent changes in mitochondrial homeostasis and cytoplasmic viscosity in mouse peripheral neurons.

Mitochondria are dynamic bioenergetic hubs that become compromised with age. In neurons, declining mitochondrial axonal transport has been associated with reduced cellular health. However, it is still unclear to what extent the decline of mitochondrial transport and function observed during ageing are coupled, and if somal and axonal mitochondria display compartment-specific features that make them more susceptible to the ageing process. It is also not known whether the biophysical state of the cytoplasm, thought to affect many cellular functions, changes with age to impact mitochondrial trafficking and homeostasis. Focusing on the mouse peripheral nervous system, we show that age-dependent decline in mitochondrial trafficking is accompanied by reduction of mitochondrial membrane potential and intramitochondrial viscosity, but not calcium buffering, in both somal and axonal mitochondria. Intriguingly, we observe a specific increase in cytoplasmic viscosity in the neuronal cell body, where mitochondria are most polarised, which correlates with decreased cytoplasmic diffusiveness. Increasing cytoplasmic crowding in the somatic compartment of DRG neurons grown in microfluidic chambers reduces mitochondrial axonal trafficking, suggesting a mechanistic link between the regulation of cytoplasmic viscosity and mitochondrial dynamics. Our work provides a reference for studying the relationship between neuronal mitochondrial homeostasis and the viscoelasticity of the cytoplasm in a compartment-dependent manner during ageing.

Three-dimensional analysis of hydrogel-imbedded aortic valve interstitial cell shape and its relation to contractile behavior.

Cell-shape is a conglomerate of mechanical, chemical, and biological mechanisms that reflects the cell biophysical state. In a specific application, we consider aortic valve interstitial cells (AVICs), which maintain the structure and function of aortic heart valve leaflets. Actomyosin stress fibers help determine AVIC shape and facilitate processes such as adhesion, contraction, and mechanosensing. However, detailed 3D assessment of stress fiber architecture and function is currently impractical. Herein, we assessed AVIC shape and contractile behaviors using hydrogel-based 3D traction force microscopy to intuit the orientation and behavior of AVIC stress fibers. We utilized spherical harmonics (SPHARM) to quantify AVIC geometries through three days of incubation, which demonstrated a shift from a spherical shape to forming substantial protrusions. Furthermore, we assessed changes in post-three day AVIC shape and contractile function within two testing regimes: (1) normal contractile level to relaxation (cytochalasin D), and (2) normal contractile level to hyper-contraction (endothelin-1). In both scenarios, AVICs underwent isovolumic shape changes and produced complex displacement fields within the hydrogel. AVICs were more elongated when relaxed and more spherical in hyper-contraction. Locally, AVIC protrusions contracted along their long axis and expanded in their circumferential direction, indicating predominately axially aligned stress fibers. Furthermore, the magnitude of protrusion displacements was correlated with protrusion length and approached a consistent displacement plateau at a similar critical length across all AVICs. This implied that stress fiber behavior is conserved, despite great variations in AVIC shapes. We anticipate our findings will bolster future investigations into AVIC stress fiber architecture and function. STATEMENT OF SIGNIFICANCE: Within the aortic valve there exists a population of aortic valve interstitial cells, which orchestrate the turnover, secretion, and remodeling of its extracellular matrix, maintaining tissue integrity and ultimately sustaining the proper mechanical function. Alterations in these processes are thought to underlie diseases of the aortic valve, which affect hundreds of thousands domestically and world-wide. Yet, to date, there are no non-surgical treatments for aortic heart valve disease, in part due to our limited understanding of the underlying disease processes. In the present study, we built upon our previous study to include a full 3D analysis of aortic valve interstitial cell shapes at differing contractile levels. The resulting detailed shape and deformation analysis provided insight into the underlying stress-fiber structures and mechanical behaviors.

Analytical device miniaturization for the detection of circulating biomarkers.

Diverse (sub)cellular materials are secreted by cells into the systemic circulation at different stages of disease progression. These circulating biomarkers include whole cells, such as circulating tumour cells, subcellular extracellular vesicles and cell-free factors such as DNA, RNA and proteins. The biophysical and biomolecular state of circulating biomarkers carry a rich repertoire of molecular information that can be captured in the form of liquid biopsies for disease detection and monitoring. In this Review, we discuss miniaturized platforms that allow the minimally invasive and rapid detection and analysis of circulating biomarkers, accounting for their differences in size, concentration and molecular composition. We examine differently scaled materials and devices that can enrich, measure and analyse specific circulating biomarkers, outlining their distinct detection challenges. Finally, we highlight emerging opportunities in biomarker and device integration and provide key future milestones for their clinical translation.

Macroscopic dynamics of neural networks with heterogeneous spiking thresholds.

Mean-field theory links the physiological properties of individual neurons to the emergent dynamics of neural population activity. These models provide an essential tool for studying brain function at different scales; however, for their application to neural populations on large scale, they need to account for differences between distinct neuron types. The Izhikevich single neuron model can account for a broad range of different neuron types and spiking patterns, thus rendering it an optimal candidate for a mean-field theoretic treatment of brain dynamics in heterogeneous networks. Here we derive the mean-field equationsfor networks of all-to-all coupled Izhikevich neurons with heterogeneous spiking thresholds. Using methods from bifurcation theory, we examine the conditions under which the mean-field theory accurately predicts the dynamics of the Izhikevich neuron network. To this end, we focus on three important features of the Izhikevich model that are subject here to simplifying assumptions: (i) spike-frequency adaptation, (ii) the spike reset conditions, and (iii) the distribution of single-cell spike thresholds across neurons. Our results indicate that, while the mean-field model is not an exact model of the Izhikevich network dynamics, it faithfully captures its different dynamic regimes and phase transitions. We thus present a mean-field model that can represent different neuron types and spiking dynamics. The model comprises biophysical state variables and parameters, incorporates realistic spike resetting conditions, and accounts for heterogeneity in neural spiking thresholds. These features allow for a broad applicability of the model as well as for a direct comparison to experimental data.

Mapping of total suspended solids using Landsat imagery and machine learning

The main objective of this work is to propose a new technique for water quality parameters monitoring by applying artificial intelligence methods to optimize remote sensing data processing. A multiple regression model was developed to create a total suspended solids (TSS) prediction model, using unsupervised machine learning. Currently, water bodies throughout the world are poorly supervised in terms of quality, so it is necessary to implement efficient mechanisms to obtain synoptic information for a good diagnosis in TSS evolution, because they are a key indicator of the biophysical state of lakes and an essential marker for continuous monitoring. Conventional methods used to monitor the physical parameters of water bodies, for example, in situ sampling, have proven impractical due to time, cost and space constraints, and remote sensing tools can help to achieve this purpose more efficiently. The proposed multiple regression model requires calibration and to that end, Lake Chapala data from the monitoring time series collected by the National Water Commission (CONAGUA) were used. Lake Chapala is the largest freshwater body in Mexico, and the human intervention that develops around the lake has caused drastic changes such as decrease in the size of the lake and increase in suspended matter and aquatic vegetation. These changes alter the balance of the system, endangering the health of the lake. This work presents a generalized semi-empirical model that uses Landsat image data and machine learning methods for estimating total suspended solids (TSS) in water bodies, with a good prediction precision (R = 0.81, RMSE = 32.52).

Analysis of Fast Fluorescence Kinetics of a Single Cyanobacterium Trapped in an Optical Microcavity.

Photosynthesis is one the most important biological processes on earth, producing life-giving oxygen, and is the basis for a large variety of plant products. Measurable properties of photosynthesis provide information about its biophysical state, and in turn, the physiological conditions of a photoautotrophic organism. For instance, the chlorophyll fluorescence intensity of an intact photosystem is not constant as in the case of a single fluorescent dye in solution but shows temporal changes related to the quantum yield of the photosystem. Commercial photosystem analyzers already use the fluorescence kinetics characteristics of photosystems to infer the viability of organisms under investigation. Here, we provide a novel approach based on an optical Fabry-Pérot microcavity that enables the readout of photosynthetic properties and activity for an individual cyanobacterium. This approach offers a completely new dimension of information, which would normally be lost due to averaging in ensemble measurements obtained from a large population of bacteria.

To the biofield theory

For a generalized analysis of the biophysical state of the human body and other living beings, the concept of the ultimate perfection of living organisms, their systemic nature is proposed, what reveals unexpected physical consequences: the basis for the existence of biofields and biorhythms, their role in homeostasis, a function of hematopoietic iron in strengthening the biofield and in the accumulation of vital information in organisms. Due to the lack of a sufficient experimental base for fundamental biophysical research, argumentations of such effects use physical logic and connection with current ideas.

Factors Affecting Community-Managed Forest Health

Forest quality is essential to be comprehended as a healthy forest would provide various benefits. The quality of forests may be found through the measurement of forest health. Internal and external factors could be measured to determine the level of forest health. Internal factors are factors related to the biophysical state of the forest ecosystem, whereas external factors are related to the manager's state. Forest health could be identified in forests managed by communities, such as forest areas managed by the Sustainable Community Forest System Group (SHK) located at Teluk Pandan District, Pesawaran Regency, Lampung Province. This study aims to identify internal and external factors related to the conservation forests' health managed by SHK Lestari. This research utilized the multiple linear analysis method. The results indicated internal factors that improved the forest health levels are biodiversity indicators, in which the parameter is tree type diversity index (H'), the vitality indicators, in which the parameter is tree damage (Cluster-plot Level Index - CLI) and visual crown ratio (VCR), as well as tread quality index, in which parameter is soil pH value. External factors that affect forest health levels are farmers' level of knowledge (FKL), farmers' motivation (FMo), and farmers' participation (FP).

A Size-Cuttable, Skin-Interactive Wearable Sensor for Digital Deciphering of Epidermis Wavy Deformation.

Body shape and curvature are vital criteria for judging health. However, few studies exist on the curvature of the body. We present a skin-interactive electronic sticker that digitally decodes the epidermis deformation in a hybrid cartridge format (disposable bandages and non-disposable kits). The device consists of two functional modes: (1) as a thin electronic sticker of 76 μm thickness and a node pitch of 7.45 mm for the measurement of body curvature in static mode, and (2) as a wrist bandage for the deciphering of skin wave fluctuations into a colored core-line map in dynamic mode. This method has high detection sensitivity in the static mode and high accuracy of 0.986 in the dynamic mode, resulting in an F1 score of 0.966 in testing by feedforward deep learning. The results show that the device can decipher 32 delicate finger folding gestures by measuring skin depths and positions via image segmentation, leading to an optimal core line in a color map. This approach can help provide a better understanding of skin wave deflection and fluctuations for potential wearable applications, such as in delicate skin-related gesture control in the metaverse, rehabilitation programs for the brain-degenerate, and as a detector of biophysical state relating to body shape and curvature in the field of digital medicine.

The nucleus as a mechanosensitive controller of cell behavior

Mechanical forces within tissues can induce cell deformation and, as a consequence, influence cell dynamics and the cell’s biophysical state. In confined environments or during migration, cells can experience high degree of compression that has been shown to induce myosin II activation, to increase cellular contractility and to trigger a transformation into a fast-amoeboid migration mode in various cell types. How single cells decode changes in their shape and respond to those by regulating their contractility setpoint remained unclear.

Advanced Software, applied with the Polygraph technique, is useful to interpret electrochemical signals, emitted from Superior Plants (Gymnosperms), during the Depatterning procedure, with the aim to alter the biophysical state, of the same vegetal, and interpret elaborations through a procedure of reverse engineering

Background: Plant organisms, in addition to electrochemical communication, which occurs both between plants belonging to the same species and between plants belonging to different species, are also supposed to communicate through other means, defined by the discipline known as Plant Neurobiology. Acting with the method called Depatterning, defined by the Canadian psychiatrist D.E. Cameron, and used as a Reverse Engineering procedure, the aim is to cancel the "consciousness" of the vegetable, to understand if they are in possession of the same consciousness. Methods: A plant organism, Dracaena fragrans, was connected to a digital polygraph, in order to monitor its parameters and, successively, doses of a psychotropic compound such as N, N-Dimethyltryptamine (N, N-DMT), and electrical impulses supplied by a Tesla coil. By interfacing directly with the plant, through direct questions, and waiting for the computerized re-elaboration of the answer, data relating to Plant Depatterning were obtained. Results: The computerized processing of the alteration of the responses provided by the polygraph (vegetable connected to the polygraph), with respect to the control condition, has made it possible to define the significance of the effect of both the psychotropic compound and the electrical discharges, in the alteration of the same responses. Conclusions: Based on the interpretation of the data obtained, it is possible to affirm the positive effect of the Depatterning procedure, in the alteration of the biophysical state of the plant.

Modelling seasonal environmental preferences of tropical tuna purse seine fisheries in the Mozambique Channel

The spatial-temporal environmental preferences and biomass aggregation of tropical tuna from purse seine fishery in the Mozambique Channel (MZC) have barely been investigated. In this study, tuna biomass volume from Fish Aggregating Devices (FADs) and Free-Swimming Schools (FSC), collected by Spanish fishing logbooks during 2003–2013, were modelled separately as a function of a set of oceanographic variables (sea surface temperature, sea surface height, geostrophic currents, salinity, and chlorophyll-a) using Generalized Additive Models (GAMs). Temporal variables (natural day, month and year), and spatial variables (latitude and longitude) were included in the models to account for the spatio-temporal structure of dynamic biomass of tropical tuna volume gathering. Oceanographic, temporal and spatial effects on aggregated catches differed between fishing modes, even though some common aspects appeared along the area and the period of study. Fishable patches of tuna biomass accumulation were explained by sea surface temperature, productivity, sea surface height, geostrophic currents, and apart from the spatio-temporal variables interactions. Although the models predicted slight differences for tuna fishing spots preferences, both fishing modes partially overlapped. Goodness of fit for selected variables showed that models were able to predict tuna catches assembled patterns in the MZC reasonably well. These results highlight a connection between the biophysical state of the oceans and purse seine tuna catches in the MZC, and ultimately may contribute to the scientific advice for the appropriate management and conservation of the exploited resources by purse seine fleets in the area of MZC.

Effects of excessive water extraction on groundwater ecosystem services: Vulnerability assessments using biophysical approaches

In this research, a systematic, integrated framework was developed to evaluate the biophysical state and vulnerability intensity of groundwater supply ecosystem service (GSES) regarding excessive groundwater withdrawal in the Mashhad plain located in the northeastern of Khorasan Razavi province in Iran. At first, following an indexing approach, the biophysical aspects of the ecosystem, including capacity, flow, and the benefits of GSES, were analyzed. Afterward, the relationship between the capacity and flow ecosystem service (ES) was assessed to identify ecosystem's sustainability status. Furthermore, GSES stability was spatially shown. Finally, GSES vulnerability and its associated ESs was assessed based on 3D model of vulnerability via indexing three components of exposure, sensitivity, and adaptive capacity. The final map spatially indicated the zoning of groundwater ecosystem services’ vulnerability intensity in Mashhad Plain. The outcomes indicate a high and very high vulnerability in more than 35% of studying area. The results indicate that about 18%, 30%, and 15% of studying land show moderate, low, and no vulnerability, respectively. Finally, it was observed that due to groundwater's over-extraction, supplying the aquifer ecosystem services was disrupted. This method can be used as a solution for the sustainable management of groundwater resources, especially in the arid and semi-arid countries facing the depletion of water resources.

Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional

The airway epithelium serves as the interface between the host and external environment. In many chronic lung diseases, the airway is the site of substantial remodeling after injury. While, idiopathic pulmonary fibrosis (IPF) has traditionally been considered a disease of the alveolus and lung matrix, the dominant environmental (cigarette smoking) and genetic (gain of function MUC5B promoter variant) risk factor primarily affect the distal airway epithelium. Moreover, airway-specific pathogenic features of IPF include bronchiolization of the distal airspace with abnormal airway cell-types and honeycomb cystic terminal airway-like structures with concurrent loss of terminal bronchioles in regions of minimal fibrosis. However, the pathogenic role of the airway epithelium in IPF is unknown. Combining biophysical, genetic, and signaling analyses of primary airway epithelial cells, we demonstrate that healthy and IPF airway epithelia are biophysically distinct, identifying pathologic activation of the ERBB-YAP axis as a specific and modifiable driver of prolongation of the unjammed-to-jammed transition in IPF epithelia. Furthermore, we demonstrate that this biophysical state and signaling axis correlates with epithelial-driven activation of the underlying mesenchyme. Our data illustrate the active mechanisms regulating airway epithelial-driven fibrosis and identify targets to modulate disease progression.

The phase separation-dependent FUS interactome reveals nuclear and cytoplasmic function of liquid-liquid phase separation.

Liquid–liquid phase separation (LLPS) of proteins and RNAs has emerged as the driving force underlying the formation of membrane-less organelles. Such biomolecular condensates have various biological functions and have been linked to disease. The protein Fused in Sarcoma (FUS) undergoes LLPS and mutations in FUS have been causally linked to the motor neuron disease Amyotrophic Lateral Sclerosis (ALS-FUS). LLPS followed by aggregation of cytoplasmic FUS has been proposed to be a crucial disease mechanism. However, it is currently unclear how LLPS impacts the behaviour of FUS in cells, e.g. its interactome. Hence, we developed a method allowing for the purification of LLPS FUS-containing droplets from cell lysates. We observe substantial alterations in the interactome, depending on its biophysical state. While non-LLPS FUS interacts mainly with factors involved in pre-mRNA processing, LLPS FUS predominantly binds to proteins involved in chromatin remodelling and DNA damage repair. Interestingly, also mitochondrial factors are strongly enriched with LLPS FUS, providing a potential explanation for the observed changes in mitochondrial gene expression in mouse models of ALS-FUS. In summary, we present a methodology to investigate the interactomes of phase separating proteins and provide evidence that LLPS shapes the FUS interactome with implications for function and disease.

On the Three-Dimensional Correlation Between Myofibroblast Shape and Contraction.

Myofibroblasts are responsible for wound healing and tissue repair across all organ systems. In periods of growth and disease, myofibroblasts can undergo a phenotypic transition characterized by an increase in extracellular matrix (ECM) deposition rate, changes in various protein expression (e.g., alpha-smooth muscle actin (αSMA)), and elevated contractility. Cell shape is known to correlate closely with stress-fiber geometry and function and is thus a critical feature of cell biophysical state. However, the relationship between myofibroblast shape and contraction is complex, even as well in regards to steady-state contractile level (basal tonus). At present, the relationship between myofibroblast shape and basal tonus in three-dimensional (3D) environments is poorly understood. Herein, we utilize the aortic valve interstitial cell (AVIC) as a representative myofibroblast to investigate the relationship between basal tonus and overall cell shape. AVICs were embedded within 3D poly(ethylene glycol) (PEG) hydrogels containing degradable peptide crosslinkers, adhesive peptide sequences, and submicron fluorescent microspheres to track the local displacement field. We then developed a methodology to evaluate the correlation between overall AVIC shape and basal tonus induced contraction. We computed a volume averaged stretch tensor ⟨U⟩ for the volume occupied by the AVIC, which had three distinct eigenvalues (λ1,2,3=1.08,0.99, and 0.89), suggesting that AVIC shape is a result of anisotropic contraction. Furthermore, the direction of maximum contraction correlated closely with the longest axis of a bounding ellipsoid enclosing the AVIC. As gel-imbedded AVICs are known to be in a stable state by 3 days of incubation used herein, this finding suggests that the overall quiescent AVIC shape is driven by the underlying stress-fiber directional structure and potentially contraction level.

In situ Sub-Cellular Identification of Functional Amyloids in Bacteria and Archaea by Infrared Nanospectroscopy.

Formation of amyloid structures is originally linked to human disease. However, amyloid materials are found extensively in the animal and bacterial world where they stabilize intra- and extra-cellular environments like biofilms or cell envelopes. To date, functional amyloids have largely been studied using optical microscopy techniques in vivo, or after removal from their biological context for higher-resolution studies in vitro. Furthermore, conventional microscopies only indirectly identify amyloids based on morphology or unspecific amyloid dyes. Here, the high chemical and spatial (≈20 nm) resolution of Infrared Nanospectroscopy (AFM-IR) to investigate functional amyloid from Escherichia coli (curli), Pseudomonas (Fap), and the Archaea Methanosaeta (MspA) in situ is exploited. It is demonstrated that AFM-IR identifies amyloid protein within single intact cells through their cross β-sheet secondary structure, which has a unique spectroscopic signature in the amide I band of protein. Using this approach, nanoscale-resolved chemical images and spectra of purified curli and Methanosaeta cell wall sheaths are provided. The results highlight significant differences in secondary structure between E. coli cells with and without curli. Taken together, these results suggest that AFM-IR is a new and powerful label-free tool for in situ investigations of the biophysical state of functional amyloid and biomolecules in general.

3D Contractile Responses of Normal and Diseased Human Aortic Valve Interstitial Cells

Objective: The bicuspid aortic valve (BAV) contains two rather than the normal three leaflets; and is actually a spectrum of structural anomalies that can include a raphe region. For reasons that remain unclear, BAVs calcify faster than normal aortic valves (NAVs). Structural remodeling in BAV is driven by aortic valve interstitial cells (AVICs) that can become activated due to mechanical and biochemical cues. Increased contractility is a hallmark of activation and reflects AVIC biophysical state. In this study, we assessed the 3D contractile responses of AVICs extracted from BAVs and NAVs to develop an improved understanding of their intrinsic function and differences. Methods: AVICs from the raphe and non-raphe regions of human BAVs were assessed. AVICs from human NAVs served as controls. AVICs and fluorescent microbeads were seeded within PEG hydrogels. Image stacks of an AVIC and surrounding fluorescent microbeads were obtained within normal and relaxed (CytochalasinD) conditions. The positions of the beads were tracked between each image stack using a custom software which output local hydrogel displacements (Figure 1A-C). Results: AVICs from BAVs produced lower levels of hydrogel displacements than NAVs (Figure 1D). Interestingly, AVICs from the raphe and non-raphe regions produced similar levels of displacements. AVICs produced complex displacement fields with regions of contraction and expansion. Furthermore, contractile displacements occurred at cell pseudopods whereas expansive displacements occurred near the mid-section of the cell. Conclusions: Contractile behaviors differed substantially between BAVs and NAVs, which suggests that AVICs are intrinsically different between the two valve types. This result suggests that AVICs are fundamentally different and that the larger BAV disorder affects the cellular scale as well as the organ-level anatomy, and will lay basis for future cellular-based therapies.

Can mechanical forces attune heterotypic cell-cell communications?

Heterotypic cell lineages relentlessly exchange biomechanical signals among themselves in metazoan organs. Hence, cell–cell communications are pivotal for organ physiology and pathogenesis. Every cell lineage of an organ responds differently to a specific signal due to its unique receptibility and signal interpretation capacity. These distinct cellular responses generate a system-scale signaling network that helps in generating a specific organ phenotype. Although the reciprocal biochemical signal exchange between non-identical neighboring cells is known to be an essential factor for organ functioning, if, then how, mechanical cues incite these signals is not yet quite explored. Cells within organ tissues experience multiple mechanical forces, such as stretching, bending, compression, and shear stress. Forms and magnitudes of mechanical forces influence biochemical signaling in a cell-specific manner. Additionally, the biophysical state of acellular extracellular matrix (ECM) can transmit exclusive mechanical cues to specific cells of an organ. As it scaffolds heterotypic cells and tissues in close proximities, therefore, ECM can easily be contemplated as a mechanical conduit for signal exchange among them. However, force-stimulated signal transduction is not always physiological, aberrant force sensing by tissue-resident cells can transduce anomalous signals to each other, and potentially can promote pathological phenotypes. Herein, I attempt to put forward a perspective on how mechanical forces may influence signal transductions among heterotypic cell populations and how they feedback each other to achieve a transient or perpetual alteration in metazoan organs. A mechanistic insight of organ scale mechanotransduction can emanate the possibility of finding potential biomarkers and novel therapeutic strategies to deal with pathogenesis and organ regeneration.

Melatonin and biological membrane bilayers: a never ending amity

Biological membrane, the most fluidic structure of a cell or an organelle, refrains the cells to progress toward apoptosis by sustaining their optimum environment. This bilayer-membrane equips all machineries required for cellular communication, limits the entry of foreign bodies, selectively transports molecules or ions depending on the need of the system but, it also acts as a first line defense against environmental insults. Due to the presence of a vast number of poly unsaturated fatty acids (PUFA), the biological membrane is highly prone to oxidative stress and as a consequence, acceleration in lipid peroxidation by free radicals, becomes a threat to cellular viability. Alterations in the biophysical state of bilayer caused by oxidative stress frequently occur in the in vivo as well as in vitro conditions. It has been well documented that the molecule, melatonin, exhibits profound coherence in neutralizing oxidative stress and thus, to normalize fluidity status of biological membranes. Aging associated decline in melatonin level with subsequent ascended lipid peroxidation and membrane viscosity found in almost all organisms further suggest the importance of melatonin in this context. Since disruption of membrane structure or even some modifications will cause a spectrum of diseases, keeping membrane intactness would be an adequate strategy to prevent these diseases. Considering the high permeability, safe and potent antioxidant capacity of melatonin, this molecule can be a superlative choice to alleviate membrane bilayer rigidity and its related ailments.