Biology subjects

Chakrabarti, B.

Publications and source records attributed to Chakrabarti, B..

At least 19 recordsLinked to original sources

bioRxiv2026

Linker stretching optimizes bonding entropy in sticker-spacer condensates

Phase separating biopolymers are often described by the sticker-spacer model, which accounts for non-attractive linkers that connect discrete attractive moieties. "Associative polymer" theories describe these systems as two coexisting fluids of stickers and spacers, respectively. In such theories the stickers and spacers are decoupled in the sense that sticker binding does not affect spacer conformations or vice versa. Informed by coarse-grained simulations, we develop a phenomenological mean-field theory to determine the microscopic coupling between the sticker and spacer degrees of freedom. Accounting for linkers connecting adjacent spacers introduces free energy contributions due to conformational entropy of the spacer and the binding combinatorics of the stickers. These contributions have opposite dependencies on spacer length because longer spacers allow a greater volume to search for binding partners but incur a greater entropy cost upon bond formation. The length dependent terms from these contributions cancel leaving a length-independent elastic term arising from the fact that a small amount of spacer stretching lowers the free energy by increasing the number of possible binding partners. The cancellation of spacer length from the theory justifies the decoupling approximation and supports mean-field treatments of heterogeneous spacers.

biophysics↗

bioRxiv2026

Gut Microbiota Signatures of Brain and Peripheral gamma-amino butyric acid (GABA) in Healthy Adult Males

Gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the mature human nervous system, plays a central role in neurodevelopment, emotion regulation, and sensory processing. Many psychiatric drugs act on the GABAergic system, highlighting its importance for healthy brain function. Individual differences in brain and circulating GABA levels have traditionally been attributed to genetic variation. However, several gut bacteria produce neuroactive compounds, including GABA, raising the possibility that microbial variation influences peripheral and central GABA levels and related measures in humans. This relationship remains largely unexplored. In a cross-sectional study of 251 healthy adults, we investigated associations between gut microbiota composition, central and peripheral GABA, and associated features. Brain GABA was quantified using magnetic resonance spectroscopy, blood GABA using enzyme-linked immunosorbent assays, and gut microbiota profiles using absolute and relative abundance measures derived from Flow Cytometry Fluorescent In Situ Hybridisation and 16S rRNA gene sequencing. Motor cortex GABA+ levels were positively associated with greater numbers of Bacteroides/Prevotella bacteria. A similar association was observed for blood GABA, which was additionally associated with greater numbers of lactic acid bacteria, Eubacterium rectale/Clostridium coccoides, and Clostridium histolyticum groups, and with predicted microbial gene pathways involved in GABA, propionate, and butyrate biosynthesis. No association was observed between brain and blood GABA concentrations. These findings provide new evidence for relationships between gut bacterial groups and central and peripheral GABA pools, supporting future longitudinal studies of causal links between gut microbiota and host GABA levels, as well as the potential for future intervention studies to influence GABAergic processing.

neuroscience↗

bioRxiv2026

Osmotically Induced Shape Changes in Membrane Vesicles

We develop a self-consistent free-energy framework in which membrane shape and osmotic pressure are determined simultaneously in a finite reservoir by minimizing bending elasticity and solute entropy. Solute conservation makes osmotic pressure a thermodynamic variable rather than an externally prescribed parameter, producing a nonlinear coupling between membrane mechanics and solvent entropy. This coupling modifies the classical stability condition for spherical vesicles: instability emerges from global free-energy competition rather than the linear Helfrich stability criterion. The resulting critical pressures differ by orders of magnitude from Helfrich predictions and agree with simulations for small and large unilamellar vesicles. The framework is relevant to cellular environments involving biomolecular condensate confinement as well as synthetic vesicles and the development of osmotic-pressure-driven encapsulation platforms.

biophysics↗

bioRxiv2025

The physical consequences of sperm gigantism

The male fruit fly produces [~] 1.8 mm long sperm, thousands of which can be stored until mating in a [~] 200 {micro}m sac, the seminal vesicle [1, 2]. While the evolutionary pressures driving such extreme sperm (flagellar) lengths have long been investigated [3-7], the physical consequences of their gigantism are unstudied. Through high-resolution three-dimensional reconstructions of in vivo sperm morphologies and rapid live imaging, we discovered that stored sperm are organized into a dense and highly aligned state. The packed flagella exhibit system-wide collective material flows, with persistent and slow-moving topological defects; individual sperm, despite their extraordinary lengths, propagate rapidly through the flagellar material, moving in either direction along material director lines. To understand how these collective behaviors arise from the constituents nonequilibrium dynamics, we conceptualize the motion of individual sperm as topologically confined to a reptation-like tube formed by its neighbors. Therein, sperm propagate through observed amplitude-constrained and internally driven flagellar bending waves, pushing off counter-propagating neighbors. From this conception, we derive a continuum theory that produces an extensile material stress that can sustain an aligned flagellar material [8-10]. Experimental perturbations and simulations of active elastic filaments verify our theoretical predictions. Our findings suggest that active stresses in the flagellar material maintain the sperm in an unentangled, hence functional state, in both sexes, and establish giant sperm in their native habitat as a novel and physiologically relevant active matter system.

biophysics↗

bioRxiv2025

Breathe in, breathe out: Bacterial density determines collective migration in aerotaxis

Bacteria navigate their environment by biasing their swimming direction toward beneficial chemicals and away from harmful ones. Out of all the chemicals bacteria respond to, oxygen stands out due to its ubiquitous presence, distinct influence on bacterial metabolism and motility, and historical role in chemotaxis research. However, a coherent understanding of bacterial motility in oxygen gradients, known as aerotaxis, remains elusive, as evidenced by conflicting reports on the migration direction of the model organism Escherichia coli in self-generated oxygen gradients. Here, by combining experiments, simulations, and theory, we provide a unified framework elucidating the fundamental biophysical principle governing bacterial aerotaxis. We track the migration of bacteria in a capillary channel under self-generated oxygen gradients and show that the migration direction depends on the overall bacterial density. At high densities, bacteria migrate toward regions of higher oxygen concentration, whereas at low densities, they move in the opposite direction. We identify a critical bacterial density at which collective migration ceases, despite the presence of oxygen gradients. A kinetic theory, based on the assumption that bacteria seek an optimal oxygen concentration, is then developed to quantitatively explain our experimental findings. We validate this hypothesis by demonstrating the biased movement of individual bacteria in a dense suspension and proposing a signaling pathway that enables this behavior. Thus, by bridging the molecular level understanding of the signaling pathway, the motility of single bacteria in oxygen gradients, and the collective population dynamics shaped by oxygen diffusion and consumption, our study provides a comprehensive understanding of aerotaxis, addressing the long-standing controversy over how bacteria response to non-uniform oxygen distributions pervasive in microbial habitats.

biophysics↗

bioRxiv2022

A chemomechanical model of sperm locomotion reveals two modes of swimming

The propulsion of mammalian spermatozoa during reproduction relies on the spontaneous periodic oscillation of their flagella. These oscillations are driven internally by the coordinated action of ATP-powered dynein motors that exert active sliding forces between microtubule doublets, resulting in bending waves that propagate along the flagellum and enable locomotion of the cell through the viscous medium. In this work, we present a chemomechanical model of a freely swimming spermatozoon that uses a sliding-control model of the flagellar axoneme capturing the coupling of motor kinetics with elastic deformations and accounts for the effect of non-local hydrodynamic interactions between the sperm head and flagellum. Nonlinear simulations of the model equations are shown to produce realistic beating patterns and swimming trajectories, which we analyze as a function of sperm number and motor activity. Our results demonstrate that the swimming velocity does not vary monotonically with dynein activity, but instead displays two local maxima corresponding to distinct modes of swimming, each characterized by qualitatively different waveforms and trajectories.

biophysics↗

bioRxiv2021

Brain structural correlates of autistic traits across the diagnostic divide: A grey matter and white matter microstructure study

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental conditions characterised by difficulties in social interaction and communication as well as stereotyped and restricted patterns of interest. Autistic traits exist in a continuum across the general population, whilst the extreme end of this distribution is diagnosed as clinical ASD. While many studies have investigated brain structure in autism using a case-control design, few have used a dimensional approach. To add to this growing body of literature, we investigated the structural brain correlates of autistic traits in a mixed sample of adults (N=91) with and without a clinical diagnosis of autism. We examined regional brain volumes (using voxel-based morphometry and surface-based morphometry) and white matter microstructure properties (using Diffusion Tensor Imaging). Our findings show widespread grey matter differences, including in the social brain regions, and some evidence for white matter microstructure differences related to higher autistic traits. These grey matter and white matter microstructure findings from our study are consistent with previous reports and support the brain structural differences in ASD. These findings provide further support for shared aetiology for autistic traits across the diagnostic divide.

neuroscience↗

bioRxiv2021

Equilibrium morphologies of a macromolecule under soft confinement

We study equilibrium shapes and shape transformations of a confined semiflexible chain inside a soft lipid tubule using simulations and continuum theories. The deformed tubular shapes and chain conformations depend on the relative magnitude of their bending moduli. We characterise the collapsed macromolecular shapes by computing statistical quantities that probe the polymer properties at small length scales and report a prolate to toroidal coil transition for stiff chains. Deformed tubular shapes, calculated using elastic theories, agree with simulations. In conjunction with scattering studies, our work may provide a mechanistic understanding of gene encapsulation in soft structures.

biophysics↗

bioRxiv2021

Thermodynamics of droplets undergoing liquid-liquid phase separation

We study the thermodynamics of binary mixtures wherein the volume fraction of the minority component is less than the amount required to form a flat interface. Based on an explicit microscopic mean field theory, we show that the surface tension dominated equilibrium phase of a polymer mixture forms a single macroscopic droplet. A combination of elastic interactions that renormalize the surface tension, and arrests phase separation for a gel-polymer mixture, stabilize a micro-droplet phase. We compute the droplet size as a function of the interfacial tension, Flory parameter, and elastic moduli of the gel. Our results illustrate the importance of the rheological properties of the solvent in dictating the thermodynamic phase behavior of biopolymers undergoing liquid-liquid phase separation.

biophysics↗

bioRxiv2020

Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently.

neuroscience↗

bioRxiv2019

A Lamin Associated Chromatin Model for Chromosome Organization

We propose a simple model for chromatin organization based on the interaction of the chromatin fibres with Lamin proteins along the nuclear membrane. Lamin proteins are known to be a major factor that influences chromatin organization, and hence gene expression in the cells. Our polymer model explains the formation of lamin associated domains, and for heteropolymers with sequence control, can reproduce observed length distributions of LADs. In particular, lamin mediated interaction can enhance the formation of chromosome territories as well as the organization of chromatin into tightly packed heterochromatin and the loosely-packed gene-rich euchromatin regions.

biophysics↗

bioRxiv2019

How Cognitive and Affective Empathy Relate to Emotion Regulation: Divergent Patterns from Trait and Task-Based Measures

Evidence suggests that empathy and emotion regulation may be related, but few studies have directly investigated this relationship. Here we report two experiments which examined: 1) how different components of empathy (cognitive & affective) relate to the habitual use of cognitive reappraisal to regulate emotions (N=220), and 2) how these components of empathy relate to implicit reappraisal in a context-framing task (N=92). In study 1, a positive correlation between cognitive empathy and reappraisal use was observed. Affective empathy showed no relationship with reappraisal use. In study 2, participants completed an implicit reappraisal task in which previously viewed negative images were paired with either a neutralising (intended to reduce negative emotionality) or descriptive (which simply described the image) framing sentence. Participants then reported how unpleasant/pleasant each image made them feel. In contrast to study 1, a positive correlation between affective empathy and the implicit reappraisal task metric (rating of neutralising-descriptive framing conditions) was observed. There was no relationship between cognitive empathy and implicit reappraisal. These findings suggest that both components of empathy are related to reappraisal, but in different ways: Cognitive empathy is related to more deliberate use of reappraisal, while affective empathy is associated with more implicit reappraisal processes.

animal behavior and cognition↗

bioRxiv2018

The true size of placebo analgesia: Concordant neural and behavioural measures of placebo analgesia during experimental acute pain

Placebo analgesia refers to the reduction of pain following the administration of an inactive treatment. While most clinical trials compare a drug treatment against a placebo to determine the efficacy of the analgesic, most experimental studies of placebo analgesia do not include a real analgesic condition. A direct comparison of placebo against a real analgesic can inform us about the true size of the placebo effect. To this end, we aimed to provide a robust estimate of placebo analgesia by contrasting the effect of pain relief expectation from an inert cream (vaseline) against a real topical analgesic agent (lidocaine) applied on two different limbs and their respective control conditions. Pain reports and electroencephalography (EEG) responses triggered by laser nociceptive stimulation were collected. Forty typical healthy adults were enrolled in a double-blind randomized within-subject study where a standard placebo induction script of verbal suggestions in a sham medical setting was used to enhance the expectation on treatment outcome. In line with the earliest studies of placebo analgesia, majority (30 of 40) of participants was placebo responders, i.e. they reported lower pain to the placebo treatment. Placebo responders reported low pain and displayed low laser evoked potentials (LEPs) amplitude for both the analgesic and placebo treatment limbs compared to the respective control limbs. Placebo analgesia correlated positively with the amplitude of the LEPs, thus establishing convergent validity of the findings. This study provides a robust estimate of the neural and behavioural measures of placebo analgesia, in comparison to a real analgesic. These estimates can help inform the quantitative criteria for similar neural and behavioural measures in assessing the effectiveness of a real drug in placebo controlled trials.

neuroscience↗

bioRxiv2017

Systemizing is genetically correlated with autism and is genetically distinct from social autistic traits

The core diagnostic criteria for autism comprise two symptom domains - social and communication difficulties, and unusually repetitive and restricted behaviour, interests and activities. There is some evidence to suggest that these two domains are dissociable, yet, this hypothesis has not been tested using molecular genetics. We test this using a GWAS of a non-social autistic trait, systemizing (N = 51,564), defined as the drive to analyse and build systems. We demonstrate that systemizing is heritable and genetically correlated with autism. In contrast, we do not identify significant genetic correlations between social autistic traits and systemizing. Supporting this, polygenic scores for systemizing are significantly positively associated with restricted and repetitive behaviour but not with social difficulties in autistic individuals. These findings strongly suggest that the two core domains of autism are genetically dissociable, and point at how to fractionate the genetics of autism.

genetics↗

bioRxiv2017

Reprogramming, oscillations and transdifferentiation in epigenetic landscapes

Waddingtons epigenetic landscape provides a phenomenological understanding of the cell differentiation pathways from the pluripotent to mature lineage-committed cell lines. In light of recent successes in the reverse programming process there has been significant interest in quantifying the underlying landscape picture through the mathematics of gene regulatory networks. We investigate the role of time delays arising from multistep chemical reactions and epigenetic rearrangement on the cell differentiation landscape for a realistic two-gene regulatory network, consisting of selfpromoting and mutually inhibiting genes. Our work provides the first theoretical basis of the transdifferentiation process in the presence of delays, where one differentiated cell type can transition to another directly without passing through the undifferentiated state. Additionally, the interplay of time-delayed feedback and a time dependent chemical drive leads to long-lived oscillatory states in appropriate parameter regimes. This work emphasizes the important role played by time-delayed feedback loops in gene regulatory circuits and provides a framework for the characterization of epigenetic landscapes.

systems biology↗

bioRxiv2017

Perceived closeness and autistic traits modulate interpersonal vocal communication

Vocal modulation is a critical component of interpersonal communication. It not only serves as a dynamic and flexible tool for self-expression and linguistic information but also plays a key role in social behaviour. Variation in vocal modulation can be driven by individual traits of the individual interlocutors, as well as by factors relating to the dyad, such as the perceived closeness between interlocutors. Accordingly, the current study examines the role of a) individual differences in autism-related traits, and b) perceived closeness between interlocutors on vocal modulation. Since lack of appropriate vocal modulation is often associated with Autism Spectrum Disorders we also focus on autism-related individual traits. The role of these individual and dyad-level factors on vocal modulation is tested for cultural generalizability by conducting this study in three separate samples from India, Italy, and the UK. Articulatory features were extracted from recorded conversations between a total of 85 same-sex pairs of participants and correlated with their self-reported perceived closeness (CR) to the other member of the pair and with the individual Autism Spectrum Quotient (AQ). Results indicated a significant positive correlation between interpersonal closeness and articulation area in all three samples. A significant negative correlation between AQ and articulation area was observed only in the UK sample. This study thus provides novel insights into determinants of interpersonal vocal communication and a test of their cultural generalizability.

animal behavior and cognition↗

bioRxiv2017

Individual differences in responsivity to social rewards: Insights from two eye-tracking tasks

Humans generally prefer social over nonsocial stimuli from an early age. Reduced preference for social rewards has been observed in individuals with autism spectrum conditions (ASC). This preference has typically been noted in separate tasks that measure orienting toward and engaging with social stimuli. In this experiment, we used two eye-tracking tasks to index both of these aspects of social preference in in 77 typical adults. We used two measures, global effect and preferential looking time. The global effect task measures saccadic deviation toward a social stimulus (related to orienting), while the preferential looking task records gaze duration bias toward social stimuli (relating to engaging). Social rewards were found to elicit greater saccadic deviation and greater gaze duration bias, suggesting that they have both greater salience and higher value compared to nonsocial rewards. Trait empathy was positively correlated with the measure of relative value of social rewards, but not with their salience. This study thus elucidates the relationship of empathy with social reward processing.

animal behavior and cognition↗

bioRxiv2016

Looking at my own Face: Visual Processing Strategies in Physical Self-representation

We live in an age of selfies. Yet, how we look at our own faces has seldom been systematically investigated. In this study we test if visual processing of self-faces is different from other faces, using psychophysics and eye-tracking. Specifically, the association between the psychophysical properties of self-face representation and visual processing strategies involved in self-face recognition was tested. Thirty-three adults performed a self-face recognition task from a series of self-other face morphs with simultaneous eye-tracking. Participants were found to look at lower part of the face for longer duration for self-face compared to other-face. Participants with a reduced overlap between self and other face representations, as indexed by a steeper slope of the psychometric response curve for self-face recognition, spent a greater proportion of time looking at the upper regions of faces identified as self. Additionally, the association of autism-related traits with self-face processing metrics was tested, since autism has previously been associated with atypical self-processing, particularly in the psychological domain. Autistic traits were associated with reduced looking time to both self and other faces. However, no self-face specific association was noted with autistic traits, suggesting that autism-related features may be related to self-processing in a domain specific manner.

animal behavior and cognition↗