Biology subjects

Chattopadhyay, M.

Publications and source records attributed to Chattopadhyay, M..

7 recordsLinked to original sources

bioRxiv2026

Dehydration triggers anomalous subdiffusion in biomimetic cell membranes

Lipid diffusion plays a central role in shaping the structural organization of cell membranes, maintaining lipid homeostasis, and facilitating cellular transport and signaling. The lateral mobility of phospholipids in membranes depends heavily on their hydration state. Furthermore, the activation energy of diffusion increases in conditions of reduced membrane hydration, suggesting that the underlying diffusion mechanism changes upon dehydration. Using two variants of fluorescence correlation spectroscopy (point FCS and scanning FCS) and two membrane reporters, we demonstrate that mild dehydration of phase-separated biomimetic cell membranes alters the lipid diffusion mechanism, resulting in anomalous subdiffusion rather than free Brownian motion. Importantly, the anomalous diffusion parameter, , decreases significantly upon the initial reduction of the membrane hydration layer, and the effect is fully reversible upon rehydration. These observations strongly indicate the reversible shift in lipid diffusion mode rather than irreversible membrane damage. We propose that this anomalous subdiffusion is caused by the formation of temporarily immobile lipid pockets in the membrane upon dehydration. These results therefore provide important insights into the mechanism of lipid diffusion in membranes undergoing local and transient dehydration, which is an important intermediate step in various biological processes associated with membrane fusion, such as neurotransmission, fertilization, and viral entry.

biophysics↗

bioRxiv2026

Mitochondrial pyruvate import in astrocytes links anaplerosis to seizure resistance

Astrocytes are glycolytic cells that convert a substantial fraction of glucose-derived pyruvate into lactate, a metabolite implicated in supporting neuronal energy demand and modulating excitability, plasticity and memory. This view has placed astrocytic lactate production and export at the centre of astrocyte-neuron metabolic coupling, but whether mitochondrial pyruvate utilization in astrocytes is dispensable in vivo or fulfils an essential function in the intact brain remains unknown. Here we show that adult astrocyte-specific deletion of Mpc2, encoding an obligatory mitochondrial pyruvate carrier subunit, causes motor deficits, neuronal hyperexcitability and seizure-associated lethality. Metabolic profiling revealed pyruvate diversion toward alanine as an unsuccessful compensatory bypass, together with impaired tricarboxylic acid-cycle metabolism and an imbalance in neurotransmitter-related pools, including glutamate, glutamine and {gamma}-aminobutyric acid. Thus, astrocytic mitochondrial pyruvate import is not primarily required for bioenergetic purposes but acts as a non-redundant anaplerotic gate that maintains neurotransmitter homeostasis, excitation-inhibition balance and seizure resistance in vivo.

neuroscience↗

bioRxiv2026

Metabolic vulnerability is a target of the antineoplastic effect of breastfeeding.

Lactation is associated with a protective effect against breast and ovarian cancer as well as against cardiovascular diseases suggesting a systemic effect. Here, we show that the serum of lactating mice and breastfeeding mothers have targeted antineoplastic effects, while serum from virgin mice and matched post-partum but non-lactating women do not. The effect is specific to cancer cells expressing Pappalysin-A (PAPP-A), a target that is shared among diseases affected by breastfeeding. RNAseq revealed that lactating serum inhibits mitochondrial function and we found that PAPP-A alone lowers mitochondrial function, suggesting that lactation serum acts by exploiting the metabolic vulnerability of these cancer cells. Using serum proteomics, we identified corticotropin release factor (CRF) as being unique to serum of lactating women and we show that CRF alone mimics the mitochondrial and anti-tumorigenic effect of lactating serum. Blocking the CRF receptor, inhibits the protective effect of lactating serum. Since CRF has shown efficacy in the clinic in other settings, our findings raise the possibility to extend its use to mimic or enhance the protective effect of breastfeeding. SummaryWe show that the serum from lactating women has anti-cancer activity and used multi-omics approaches to identify corticotropin release factor as a peptide able to mimic the effect of lactating serum by targeting cells with low mitochondrial activity.

cancer biology↗

bioRxiv2026

Mitochondria-nucleus communication dictates progressive versus bimodal aging of the mammary gland.

Non-linear aging, identified through oscillations in human plasma proteomics around 44 and 60, is postulated to contribute to the onset of diseases. Incidence of breast cancer follows such bimodal pattern. We show that mitochondria-nucleus matching in mice results in two mammary gland aging patterns, including a bimodal pattern associated with susceptibility to mammary tumor and that this bimodal signature is enriched in breast cancer patients diagnosed at 45 and 65.

cancer biology↗

bioRxiv2023

Nanoscale structural response of biomimetic cell membranes to controlled dehydration.

Although cell membranes in physiological conditions exist in excess of water, there is a number of biochemical processes, such as adsorption of biomacromolecules or membrane fusion events, that require partial or even complete, transient dehydration of lipid membranes. Even though the dehydration process is crucial for understanding all fusion events, still little is known about the structural adaptation of the lipid membranes when their interfacial hydration layer is perturbed. Here, we introduce the study on the nanoscale structural reorganization of the phase-separated, supported lipid bilayers (SLBs) under a wide range of hydration conditions. Model lipid membranes were characterized with the combination of fluorescence microscopy and atomic force microscopy, and crucially, without applying any chemical or physical modifications, that so far have been considered to be indispensable for maintaining the membrane integrity upon dehydration. We revealed that decreasing hydration state of the membrane leads to an enhanced mixing of lipids characteristic for the liquid-disordered (Ld) phase with those forming liquid-ordered (Lo) phase. This is associated with a 2-fold decrease in the hydrophobic mismatch between the Ld and Lo lipid phases and a 3-fold decrease of line tension for the completely desiccated membrane. Importantly, the observed changes in the hydrophobic mismatch, line tension, and miscibility of lipids are fully reversible upon subsequent rehydration of the membrane. These findings provide deeper insights into the fundamental processes such as cell-cell fusion that require partial dehydration at the interface of two membranes.

biophysics↗

bioRxiv2021

Hydration layer of only few molecules controls lipid mobility in biomimetic membranes

Self-assembly of biomembranes results from the intricate interactions between water and the lipids hydrophilic head groups. Therefore, the lipid-water interplay strongly contributes to modulating membranes architecture, lipid diffusion, and chemical activity. Here, we introduce a new method of obtaining dehydrated, phase-separated, supported lipid bilayers (SLBs) solely by controlling the decrease of their environments relative humidity. This facilitates the study of the structure and dynamics of SLBs over a wide range of hydration states. We show that the lipid domain structure of phase-separated SLBs is largely insensitive to the presence of the hydration layer. In stark contrast, lipid mobility is drastically affected by dehydration, showing a 6-fold decrease in lateral diffusion. At the same time, the diffusion activation energy increases approximately twofold for the dehydrated membrane. The obtained results, correlated with the hydration structure of a lipid molecule, revealed that about 6-7 water molecules directly hydrating the phosphocholine moiety play a pivotal role in modulating lipid diffusion. These findings could provide deeper insights into the fundamental reactions where local dehydration occurs, for instance during cell-cell fusion, and help us better understand the survivability of anhydrobiotic organisms. Finally, the strong dependence of lipid mobility on the number of hydrating water molecules opens up an application potential for SLBs as very precise, nanoscale hydration sensors.

biophysics↗

bioRxiv2021

Modeling gene x environment interactions in PTSD using glucocorticoid-induced transcriptomics in human neurons

Post-traumatic stress disorder (PTSD) results from severe trauma exposure, but the extent to which genetic and epigenetic risk factors impact individual clinical outcomes is unknown. We assessed the impact of genomic differences following glucocorticoid administration by examining the transcriptional profile of human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons and live cultured peripheral blood mononuclear cells from combat veterans with PTSD (n=5) and without PTSD (n=5). This parallel examination in baseline and glucocorticoid-treated conditions resolves cell-type specific and diagnosis-dependent elements of stress response, and permits discrimination of gene expression signals associated with PTSD risk from those induced by stress. Computational analyses revealed neuron-specific glucocorticoid-response expression patterns that were enriched for transcriptomic patterns observed in clinical PTSD samples. PTSD-specific signatures, albeit underpowered, accurately stratify veterans with PTSD relative to combat-exposed controls. Overall, in vitro PTSD and glucocorticoid response signatures in blood and brain cells represent exciting new platforms with which to test the genetic and epigenetic mechanisms underlying PTSD, identify biomarkers of PTSD risk and onset, and conduct drug-screening to identify novel therapeutics to prevent or ameliorate clinical phenotypes.

pathology↗