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Bibhu Ranjan Sarangi

Bio: Bibhu Ranjan Sarangi is an academic researcher from Paris Diderot University. The author has contributed to research in topics: Biological membrane & Lipid bilayer. The author has an hindex of 6, co-authored 7 publications receiving 627 citations. Previous affiliations of Bibhu Ranjan Sarangi include Curie Institute & SRM University.

Papers
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Journal ArticleDOI
TL;DR: A microfluidic technique to produce 3D cell-based assays and to interrogate the interplay between tumor growth and mechanics in vitro, suggesting that mechanical cues from the surrounding microenvironment may trigger cell invasion from a growing tumor.
Abstract: Deciphering the multifactorial determinants of tumor progression requires standardized high-throughput preparation of 3D in vitro cellular assays. We present a simple microfluidic method based on the encapsulation and growth of cells inside permeable, elastic, hollow microspheres. We show that this approach enables mass production of size-controlled multicellular spheroids. Due to their geometry and elasticity, these microcapsules can uniquely serve as quantitative mechanical sensors to measure the pressure exerted by the expanding spheroid. By monitoring the growth of individual encapsulated spheroids after confluence, we dissect the dynamics of pressure buildup toward a steady-state value, consistent with the concept of homeostatic pressure. In turn, these confining conditions are observed to increase the cellular density and affect the cellular organization of the spheroid. Postconfluent spheroids exhibit a necrotic core cemented by a blend of extracellular material and surrounded by a rim of proliferating hypermotile cells. By performing invasion assays in a collagen matrix, we report that peripheral cells readily escape preconfined spheroids and cell–cell cohesivity is maintained for freely growing spheroids, suggesting that mechanical cues from the surrounding microenvironment may trigger cell invasion from a growing tumor. Overall, our technology offers a unique avenue to produce in vitro cell-based assays useful for developing new anticancer therapies and to investigate the interplay between mechanics and growth in tumor evolution.

390 citations

Journal ArticleDOI
TL;DR: It is shown that rigidity sensing and adaptation emerge naturally from actin cytoskeleton remodeling, and increasing substrate stiffness correlates with the emergence of an orientational order in actin stress fibers, which exhibit an isotropic to nematic transition that is characterized quantitatively in the framework of active matter theory.
Abstract: Matrix rigidity sensing regulates a large variety of cellular processes and has important implications for tissue development and disease. However, how cells probe matrix rigidity, and hence respond to it, remains unclear. Here, we show that rigidity sensing and adaptation emerge naturally from actin cytoskeleton remodelling. Our in vitro experiments and theoretical modelling demonstrate a biphasic rheology of the actin cytoskeleton, which transitions from fluid on soft substrates to solid on stiffer ones. Furthermore, we find that increasing substrate stiffness correlates with the emergence of an orientational order in actin stress fibres, which exhibit an isotropic to nematic transition that we characterize quantitatively in the framework of active matter theory. These findings imply mechanisms mediated by a large-scale reinforcement of actin structures under stress, which could be the mechanical drivers of substrate stiffness-dependent cell shape changes and cell polarity.

231 citations

Journal ArticleDOI
TL;DR: The results reveal strong spatiotemporal correlations between vinculin tension and cell traction forces at FAs throughout a wide range of substrate stiffnesses and propose a model in which FA dynamics results from tension changes along the FAs.
Abstract: Focal adhesions (FAs) are important mediators of cell–substrate interactions. One of their key functions is the transmission of forces between the intracellular acto-myosin network and the substrate. However, the relationships between cell traction forces, FA architecture, and molecular forces within FAs are poorly understood. Here, by combining Forster resonance energy transfer (FRET)-based molecular force biosensors with micropillar-based traction force sensors and high-resolution fluorescence microscopy, we simultaneously map molecular tension across vinculin, a key protein in FAs, and traction forces at FAs. Our results reveal strong spatiotemporal correlations between vinculin tension and cell traction forces at FAs throughout a wide range of substrate stiffnesses. Furthermore, we find that molecular tension within individual FAs follows a biphasic distribution from the proximal (toward the cell nucleus) to distal end (toward the cell edge). Using super-resolution imaging, we show that such a distrib...

62 citations

Book ChapterDOI
TL;DR: This chapter provides detailed protocol for fabrication, characterization, functionalization, and use of the micropillar substrates in the study of mechanotransduction.
Abstract: Increasing evidence has shown that mechanical cues from the environment play an important role in cell biology Mechanotransduction or the study of how cells can sense these mechanical cues, and respond to them, is an active field of research However, it is still not clear how cells sense and respond to mechanical cues Thus, new tools are being rapidly developed to quantitatively study cell mechanobiology Particularly, force measurement tools such as micropillar substrates have provided new insights into the underlying mechanisms of mechanosensing In this chapter, we provide detailed protocol for fabrication, characterization, functionalization, and use of the micropillar substrates

46 citations

Journal ArticleDOI
TL;DR: In this paper, a brief overview of the phase behavior of binary and ternary lipid-cholesterol mixtures determined from these experiments is presented, and the results of recent x-ray diffraction and fluorescence microscopy studies on these systems suggest a possible resolution of the reported discrepancy in the phase behaviour of these systems obtained using different experimental techniques.

25 citations


Cited by
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Journal ArticleDOI
TL;DR: The four most commonly used spherical cancer models in cancer research are proposed based on culture methods for obtaining them and on subsequent differences in sphere biology: the multicellular tumor spheroid model, first described in the early 70s and obtained by culture of cancer cell lines under nonadherent conditions; tumorospheres, a model of cancer stem cell expansion established in a serum-free medium supplemented with growth factors.

861 citations

Journal ArticleDOI
12 Feb 2015-Cell
TL;DR: It is reported that, in the absence of focal adhesions and under conditions of confinement, mesenchymal cells can spontaneously switch to a fast amoeboid migration phenotype and, Interestingly, transformed cells are more prone to adopt this fast migration mode.

662 citations

Journal ArticleDOI
TL;DR: This review attempts to summarize the various 3D culture systems, with an emphasis on the most well characterized and widely applied model - multicellular tumor spheroids.

603 citations

Journal ArticleDOI
TL;DR: It is shown that in response to matrix rigidity and density, force transmission and transduction are explained by the mechanical properties of the actin–talin–integrin–fibronectin clutch.
Abstract: Cell function depends on tissue rigidity, which cells probe by applying and transmitting forces to their extracellular matrix, and then transducing them into biochemical signals. Here we show that in response to matrix rigidity and density, force transmission and transduction are explained by the mechanical properties of the actin-talin-integrin-fibronectin clutch. We demonstrate that force transmission is regulated by a dynamic clutch mechanism, which unveils its fundamental biphasic force/rigidity relationship on talin depletion. Force transduction is triggered by talin unfolding above a stiffness threshold. Below this threshold, integrins unbind and release force before talin can unfold. Above the threshold, talin unfolds and binds to vinculin, leading to adhesion growth and YAP nuclear translocation. Matrix density, myosin contractility, integrin ligation and talin mechanical stability differently and nonlinearly regulate both force transmission and the transduction threshold. In all cases, coupling of talin unfolding dynamics to a theoretical clutch model quantitatively predicts cell response.

543 citations

Journal ArticleDOI
TL;DR: This work has shown that the physical properties of the cellular environment, which include matrix stiffness, topography, geometry and the application of external forces, can alter collective cell behaviours, tissue organization and cell-generated forces.
Abstract: The way in which cells coordinate their behaviours during various biological processes, including morphogenesis, cancer progression and tissue remodelling, largely depends on the mechanical properties of the external environment. In contrast to single cells, collective cell behaviours rely on the cellular interactions not only with the surrounding extracellular matrix but also with neighbouring cells. Collective dynamics is not simply the result of many individually moving blocks. Instead, cells coordinate their movements by actively interacting with each other. These mechanisms are governed by mechanosensitive adhesion complexes at the cell-substrate interface and cell-cell junctions, which respond to but also further transmit physical signals. The mechanosensitivity and mechanotransduction at adhesion complexes are important for regulating tissue cohesiveness and thus are important for collective cell behaviours. Recent studies have shown that the physical properties of the cellular environment, which include matrix stiffness, topography, geometry and the application of external forces, can alter collective cell behaviours, tissue organization and cell-generated forces. On the basis of these findings, we can now start building our understanding of the mechanobiology of collective cell movements that span over multiple length scales from the molecular to the tissue level.

492 citations