Biology subjects

Sarkar, N.

Publications and source records attributed to Sarkar, N..

6 recordsLinked to original sources

bioRxiv2026

Dynein-microtubule forces drive nucleokinesis and transmigration in T cells

Beyond the mechanical capacity of canonical actomyosin-driven amoeboid motility in permissive extracellular environments, the nucleus becomes the principal barrier to T cell migration in confining tissues. We establish the dynein-microtubule (MT) force-transmission axis as an essential mechanism for nuclear translocation during confined T cell migration and transmigration. We argue that dynein acts both as a motor and as an F-actin-anchored force-transmission element (fulcrum), sliding MTs and the MT-coupled nucleus along the cell cortex to drive nucleokinesis and productive cell displacement. Dynein is the primary driver of nucleokinesis: its inhibition arrests nucleus movement independently of myosin II activity, while F-actin dynamics remain spatiotemporally decoupled from nuclear oscillations. During transmigration, dynein and actomyosin act cooperatively and non-redundantly, and only combined inhibition abolishes nuclear passage. Computational modeling demonstrates that dynein-mediated pulling, together with volume exclusion imposed by the nucleus, is sufficient to generate self-organized nuclear oscillations. Dynein inhibition in zebrafish Langerhans cells impairs protrusion dynamics in situ, identifying the dynein-MT axis as an evolutionarily conserved mechanobiological program. Collectively, these findings identify the dynein-MT mechanical unit as a potential target for engineering T cells with enhanced solid-tumor infiltration.

cell biology↗

bioRxiv2026

Mechano-sensitivity of multi-component caveolae

Caveolae are small spherical invaginations of the cell membrane with well established mechano-sensing and mechano-regulation functions. The release of caveolae components upon tension elevation is key to their mechao-signalling function. We present a thermodynamic model of caveolae stability under tension based on the phase separation of membrane-associated proteins into invaginated, multi-component membrane domains enriched in the curvature-generating membrane protein caveolin, and stabilised by the curvature-dependent binding of cytosolic proteins: members of the Cavin family which can form a rigid coat over caveolin domains, and the ATPase EHD2 which can form ring-like oligomers at the caveolae neck. This model shows that purely membrane domains show gradual release of their components upon tension elevation. Invaginations stabilised by a Cavin coat can sustain higher tensions with potentially sharp Cavin unbinding at a threshold tension but still release their membrane components smoothly upon tension increase. On the other hand, caveolae stabilised by an EHD2 ring exhibit increased mechano-protection and allow for a sharp release of membrane components. Therefore, the multi-component nature of caveolae self-organisation bestows these membrane domains with a switch-like response to tension variations which leads to the abrupt release of caveolae content beyond a well defined membrane tension threshold. Significance statementCaveolae are small invaginated domains of Caveolin proteins at the plasma membrane, stabilised by coat of Cavin proteins and a ring of EHD2 proteins at their neck. They contribute to cellular mechano-sensing by disassembling under elevated membrane tension, thereby releasing components that can regulate signalling events. Using a thermodynamic model of protein self-assembly, we show that caveolin domains disassemble smoothly under tension. While the Cavin coat affords mechanical protection without altering this gradual release, the EHD2 ring induces a switch-like release near a threshold tension, enabling acute mechano-sensing.

biophysics↗

bioRxiv2022

In silico identification of novel peptides as potential modulators of Aβ42 Amyloidogenesis

Alzheimers Disease is a neurodegenerative disease for which no cure is available at present. The presence of amyloid plaques in the extracellular space of neural cells is the key feature of this fatal disease. Amyloid-Beta (A{beta}) is a 40-42 amino acid peptide and the main component of amyloid plaques. This peptide is produced by the proteolysis of Amyloid Precursor Protein by presenilin. Deposition of 42 residual A{beta} peptides forms fibrils structure, leading to disruption of neuron synaptic transmission, inducing neural cell toxicity, ultimately leading to neuron death. To modulate the amyloidosis of A{beta} peptides, various novel peptides have been investigated via molecular docking and molecular dynamic simulation studies. The sequence-based peptides were designed and investigated for their interaction with A{beta}42 monomer and fibril using the molecular docking method, and their influence on the structural stability of target proteins was studied using molecular simulations. According to the docking results, amongst all the synthetic peptides, the peptide YRIGY (P6) has the highest binding affinity with A{beta}42 fibril, and the peptide DKAPFF (P12) shows better binding with A{beta}42 monomer. Moreover, simulation results also suggest that the higher the binding affinity, the better the inhibitory action. From these findings, it is suggested that both the peptides can modulate the amyloidogenesis, but peptide (P6) has better potential for the disaggregation of the fibrils, whereas peptide P12 stabilizes the native structure of the A{beta}42 monomer more effectively and hence can serve as a potential amyloid inhibitor. Thus, these peptides can be explored as therapeutic agents against Alzheimers Disease.

bioinformatics↗

bioRxiv2018

Field induced cell proliferation and death in a thick epithelium

We study the dynamics of a thick polar epithelium subjected to the action of both an electric and a flow field in a planar geometry. We develop a generalized continuum hydrodynamic description and describe the tissue as a two component fluid system. The cells and the interstitial fluid are the two components and we keep all terms allowed by symmetry. In particular we keep track of the cell pumping activity for both solvent flow and electric current and discuss the corresponding orders of magnitude. We study the growth dynamics of tissue slabs, their steady states and obtain the dependence of the cell velocity, net cell division rate, and cell stress on the flow strength and the applied electric field. We find that finite thickness tissue slabs exist only in a restricted region of phase space and that relatively modest electric fields or imposed external flows can induce either proliferation or death.

biophysics↗

bioRxiv2018

Test-Retest Reliability of Task-based and Resting-state Blood Oxygen Level Dependence and Cerebral Blood Flow measures

Despite their wide-spread use, only limited information is available on the comparative test-retest reliability of task-based functional and resting state magnetic resonance imaging measures of blood oxygen level dependence (tb-fMRI and rs-fMRI) and cerebral blood flow (CBF) using arterial spin labeling. This information is critical to designing properly powered longitudinal studies. Here we comprehensively quantified and compared the test-retest reliability and reproducibility performance of 8 commonly applied fMRI tasks, 6 rs-fMRI metrics and CBF in 30 healthy volunteers. We find large variability in test-retest reliability performance across the different tb-fMRI paradigms and rs-fMRI metrics, ranging from poor to excellent. A larger extent of activation in tb-fMRI is linked to higher between-subject reliability of the respective task suggesting that differences in the amount of activation may be used as a first reliability estimate of novel tb-fMRI paradigms. For rs-fMRI, a good reliability of local activity estimates is paralleled by poor performance of global connectivity metrics. Evaluated CBF measures provide in general a good to excellent test-reliability matching or surpassing the best performing tb-fMRI and rs-fMRI metrics. This comprehensive effort allows for direct comparisons of test-retest reliability between the evaluated MRI domains and measures to aid the design of future tb-fMRI, rs-fMRI and CBF studies.

neuroscience↗

bioRxiv2017

Low Rate of Somatic Mutations in a Long-Lived Oak Tree

Because plants do not possess a proper germline, deleterious somatic mutations can be passed to gametes and a large number of cell divisions separating zygote from gamete formation in long-lived plants may lead to many mutations. We sequenced the genome of two terminal branches of a 234-year-old oak tree and found few fixed somatic single-nucleotide variants (SNVs), whose sequential appearance in the tree could be traced along nested sectors of younger branches. Our data suggest that stem cells of shoot meristems are robustly protected from accumulation of mutations in trees.

plant biology↗