@article {163319, title = {Physico-chemical regulation of bacterial growth success under 3D confinement.}, journal = {Soft Matter}, year = {2026}, month = {2026 Jan 22}, abstract = {

How environmental factors influence bacterial growth remains an extensively pursued, yet perennially challenging question. Most natural bacterial habitats are complex 3D spaces, featuring disordered spatial architectures, heterogeneous nutrient availability, and broad temperature ranges. However, state-of-the-art knowledge on bacterial growth almost entirely derives from conventional experimental platforms - liquid culture and 2D flat plates - which offer limited capacity to recapitulate the diverse physico-chemical aspects intrinsic to physiological niches. Consequently, we do not fully understand how manifold environmental variables act in concert to influence growth dynamics. Here, we report the first-such interrogation of bacterial growth success under 3D confinement across combinatorial physico-chemical regimes. We accomplish this by engineering mechanically tunable viscoelastic 3D porous media, multiplexed with three distinct nutrient compositions and five different growth temperatures. Across this parameter space, we discover regimes of either confinement-driven or temperature-driven growth success, as well as nutrient composition-dependent modulation of these effects. Our work identifies a tripartite regulatory framework that captures the inter-linked effects of three generic environmental variables - mechanical constraints, nutrient availability, and temperature - on growth under 3D confinement, supported by direct experimental evidence. Together, our findings establish how environmental factors influence growth across physico-chemically complex 3D milieus.

}, issn = {1744-6848}, doi = {10.1039/d5sm01082a}, url = {https://pubmed.ncbi.nlm.nih.gov/41568648/}, author = {Bagade, Nikita and Sreepadmanabh, M and Ganesan, Gokulnath and Bhattacharjee, Tapomoy} } @article {160484, title = {Distinct Chemical Cues Reprogram Cellular and Multicellular Phenotypes in Ovarian Cancer Spheroids.}, journal = {Small}, year = {2025}, month = {2025 Sep 16}, pages = {e06120}, abstract = {

The self-organization of cellular collectives is crucial in development and cancer. Multicellular aggregation in cancer is associated with a higher efficiency of metastasis. However, it is not fully understood how mechanochemical microenvironmental cues affect the organization and stability of such ensembles. Here, using a model system of ovarian cancer spheroids, which temporally transit from solid, dysmorphic moruloids to structurally plastic, lumen-containing blastuloids, it is shown that the periodic volume fluctuations observed in blastuloids are driven by lumenal fluid influx and cell-cell junctional states. Furthermore, blastuloid cell states are reprogrammed, which enables them to rapidly recover from even complete structural disintegration and self-organize into fully lumenized ensembles. Using targeted chemical perturbations, two distinct cues are identified that regulate separate transition traits: calcium levels establish cell states cognate to, and pH regulates the fluctuation dynamics of blastuloid phenotypes. The work holds significant implications toward understanding mechanisms governing structural resilience and plasticity in complex cellular assemblies.

}, issn = {1613-6829}, doi = {10.1002/smll.202506120}, author = {Sreepadmanabh, M and Ganesh, Meenakshi and Langthasa, Jimpi and Bhat, Ramray and Bhattacharjee, Tapomoy} } @article {150944, title = {Cell shape affects bacterial colony growth under physical confinement.}, journal = {Nat Commun}, volume = {15}, year = {2024}, month = {2024 Nov 08}, pages = {9561}, abstract = {

Evidence from homogeneous liquid or flat-plate cultures indicates that biochemical cues are the primary modes of bacterial interaction with their microenvironment. However, these systems fail to capture the effect of physical confinement on bacteria in their natural habitats. Bacterial niches like the pores of soil, mucus, and infected tissues are disordered microenvironments with material properties defined by their internal pore sizes and shear moduli. Here, we use three-dimensional matrices that match the viscoelastic properties of gut mucus to test how altering the physical properties of their microenvironment influences the growth of bacteria under confinement. We find that low aspect\ ratio (spherical) bacteria form compact, spherical colonies under confinement while high aspect\ ratio (rod-shaped) bacteria push their progenies further outwards to create elongated colonies with a higher surface area, enabling increased access to nutrients. As a result, the population growth of high aspect\ ratio bacteria is, under the tested conditions, more robust to increased physical confinement compared to that of low aspect\ ratio bacteria. Thus, our experimental evidence supports that environmental physical constraints can play a selective role in bacterial growth based on cell shape.

}, keywords = {Bacteria, Cell Shape, Escherichia coli}, issn = {2041-1723}, doi = {10.1038/s41467-024-53989-6}, author = {Sreepadmanabh, M and Ganesh, Meenakshi and Sanjenbam, Pratibha and Kurzthaler, Christina and Agashe, Deepa and Bhattacharjee, Tapomoy} } @article {144784, title = {Design approaches for 3D cell culture and 3D bioprinting platforms.}, journal = {Biophys Rev (Melville)}, volume = {5}, year = {2024}, month = {2024 Jun}, pages = {021304}, abstract = {

The natural habitat of most cells consists of complex and disordered 3D microenvironments with spatiotemporally dynamic material properties. However, prevalent methods of culture study cells under poorly biomimetic 2D confinement or homogeneous conditions that often neglect critical topographical cues and mechanical stimuli. It has also become increasingly apparent that cells in a 3D conformation exhibit dramatically altered morphological and phenotypical states. In response, efforts toward designing biomaterial platforms for 3D cell culture have taken centerstage over the past few decades. Herein, we present a broad overview of biomaterials for 3D cell culture and 3D bioprinting, spanning both monolithic and granular systems. We first critically evaluate conventional monolithic hydrogel networks, with an emphasis on specific experimental requirements. Building on this, we document the recent emergence of microgel-based 3D growth media as a promising biomaterial platform enabling interrogation of cells within porous and granular scaffolds. We also explore how jammed microgel systems have been leveraged to spatially design and manipulate cellular structures using 3D bioprinting. The advent of these techniques heralds an unprecedented ability to experimentally model complex physiological niches, with important implications for tissue bioengineering and biomedical applications.

}, issn = {2688-4089}, doi = {10.1063/5.0188268}, author = {Sreepadmanabh, M and Arun, Ashitha B and Bhattacharjee, Tapomoy} } @article {142306, title = {Dynamic clustering of active rings}, journal = {Phys. Rev. Research}, volume = {6}, year = {2024}, month = {02/2024}, abstract = {

A collection of rings made of active Brownian particles (ABPs) for different packing fractions and activities is investigated using computer simulations. We show that active rings display an emergent dynamic clustering instead of the conventional motility-induced phase separation (MIPS) as in the case of collection of ABPs. Surprisingly, increasing packing fraction of rings exhibits a nonmonotonicity in the dynamics due to the formation of a large number of small clusters. The conformational fluctuations of the polymers suppress the usual MIPS exhibited by ABPs. Our findings demonstrate how the motion of a collection of rings is influenced by the interplay of activity, topology, and connectivity.

}, doi = {10.1103/PhysRevResearch.6.L012038}, author = {Theeyancheri, Ligesh and Chaki, Subhasish and Bhattacharjee, Tapomoy and Chakrabarti, Rajarshi} } @article {152149, title = {Interplay of geometry and mechanics in epithelial wound healing.}, journal = {Phys Rev E}, volume = {110}, year = {2024}, month = {2024 Nov}, pages = {054411}, abstract = {

Wound healing is a complex biological process critical for maintaining an organism{\textquoteright}s structural integrity and tissue repair following an infection or injury. Recent studies have unveiled the mechanisms involving the coordination of biochemical and mechanical responses in the tissue in wound healing. In this article, we focus on the healing property of an epithelial tissue as a material while the effects of biological mechanisms such as cell proliferation, tissue intercalation, cellular migration, cell crawling, and filopodia protrusion is minimal. We present a mathematical framework that predicts the fate of a wounded tissue based on the wound{\textquoteright}s geometrical features and the tissue{\textquoteright}s mechanical properties. Precisely, adapting the vertex model of tissue mechanics, we predict whether a wound of a specific size in an epithelial monolayer characterized by certain levels of actomyosin contractility and cell-cell adhesion will heal (i.e., close), shrink in size, or rupture the tissue further. Moreover, we show how tissue-mediated mechanisms such as purse-string tension at the wound boundary facilitate wound healing. Finally, we validate the predictions of our model by designing an experimental setup that enables us to create wounds of specific sizes in kidney epithelial cells (MDCK) monolayers. Altogether, this work sets up a basis for interpreting the interplay of mechanical and geometrical features of a tissue in the process of wound healing.

}, keywords = {Animals, Biomechanical Phenomena, Dogs, Epithelial Cells, Epithelium, Madin Darby Canine Kidney Cells, Mechanical Phenomena, Models, Biological, Wound Healing}, issn = {2470-0053}, doi = {10.1103/PhysRevE.110.054411}, author = {Babu, Nandhu Krishna and Sreepadmanabh, M and Dutta, Sayantan and Bhattacharjee, Tapomoy} } @article {131292, title = {Active dynamics of linear chains and rings in porous media.}, journal = {J Chem Phys}, volume = {159}, year = {2023}, month = {2023 Jul 07}, abstract = {

To understand the dynamical and conformational properties of deformable active agents in porous media, we computationally investigate the dynamics of linear chains and rings made of active Brownian monomers. In porous media, flexible linear chains and rings always migrate smoothly and undergo activity-induced swelling. However, semiflexible linear chains though navigate smoothly, shrink at lower activities, followed by swelling at higher activities, while semiflexible rings exhibit a contrasting behavior. Semiflexible rings shrink, get trapped at lower activities, and escape at higher activities. This demonstrates how activity and topology interplay and control the structure and dynamics of linear chains and rings in porous media. We envision that our study will shed light on understanding the mode of transport of shape-changing active agents in porous media.

}, issn = {1089-7690}, doi = {10.1063/5.0148744}, author = {Theeyancheri, Ligesh and Chaki, Subhasish and Bhattacharjee, Tapomoy and Chakrabarti, Rajarshi} } @article {128090, title = {Jammed microgel growth medium prepared by flash-solidification of agarose for 3D cell culture and 3D bioprinting.}, journal = {Biomed Mater}, year = {2023}, month = {2023 May 05}, abstract = {

Although cells cultured in 3D platforms are proven to be beneficial for studying cellular behavior in settings similar to their physiological state, due to the ease, convenience, and accessibility, traditional 2D culturing approaches are widely adopted. Jammed microgels are a promising class of biomaterials extensively suited for 3D cell culture, tissue bioengineering, and 3D bioprinting. However, existing protocols for fabricating such microgels either involve complex synthesis steps, long preparation times, or polyelectrolyte hydrogel formulations that sequester ionic elements from the cell growth media. Hence, there is an unmet need for a broadly biocompatible, high-throughput, and easily accessible manufacturing process. We address these demands by introducing a rapid, high-throughput, and remarkably straightforward method to synthesize jammed microgels composed of flash-solidified agarose granules directly prepared in a culture medium of choice. Our jammed growth media are optically transparent, porous, yield stress materials with tunable stiffness and self-healing properties, which makes them ideal for 3D cell culture as well as 3D bioprinting. The charge-neutral and inert nature of agarose make them suitable for culturing various cell types and species, the specific growth media for which do not alter the chemistry of the manufacturing process. Unlike several existing 3D platforms, these microgels are readily compatible with standard techniques such as absorbance-based growth assays, antibiotic selection, RNA extraction, and live cell encapsulation. In effect, we present a versatile, highly accessible, inexpensive, and easily adoptable biomaterial for 3D cell culture and 3D bioprinting. We envision their widespread application not just in routine laboratory settings but also in designing multicellular tissue mimics and dynamic co-culture models of physiological niches.

}, issn = {1748-605X}, doi = {10.1088/1748-605X/acd315}, author = {Sreepadmanabh, M and Ganesh, Meenakshi and Bhat, Ramray and Bhattacharjee, Tapomoy} } @article {115812, title = {Migration of active rings in porous media.}, journal = {Phys Rev E}, volume = {106}, year = {2022}, month = {2022 Jul}, pages = {014504}, abstract = {

Inspired by how the shape deformations in active organisms help them to migrate through disordered porous environments, we simulate active ring polymers in two-dimensional random porous media. Flexible and inextensible active ring polymers navigate smoothly through the disordered media. In contrast, semiflexible rings undergo transient trapping inside the pore space; the degree of trapping is inversely correlated with the increase in activity. We discover that flexible rings swell while inextensible and semiflexible rings monotonically shrink upon increasing the activity. Together, our findings identify the optimal migration of active ring polymers through porous media.

}, issn = {2470-0053}, doi = {10.1103/PhysRevE.106.014504}, author = {Theeyancheri, Ligesh and Chaki, Subhasish and Bhattacharjee, Tapomoy and Chakrabarti, Rajarshi} } @article {103921, title = {A geometric criterion for the optimal spreading of active polymers in porous media.}, journal = {Nat Commun}, volume = {12}, year = {2021}, month = {2021 Dec 06}, pages = {7088}, abstract = {

Efficient navigation through disordered, porous environments poses a major challenge for swimming microorganisms and future synthetic cargo-carriers. We perform Brownian dynamics simulations of active stiff polymers undergoing run-reverse dynamics, and so mimic bacterial swimming, in porous media. In accord with experiments of Escherichia coli, the polymer dynamics are characterized by trapping phases interrupted by directed hopping motion through the pores. Our findings show that the spreading of active agents in porous media can be optimized by tuning their run lengths, which we rationalize using a coarse-grained model. More significantly, we discover a geometric criterion for the optimal spreading, which emerges when their run lengths are comparable to the longest straight path available in the porous medium. Our criterion unifies results for porous media with disparate pore sizes and shapes and for run-and-tumble polymers. It thus provides a fundamental principle for optimal transport of active agents in densely-packed biological and environmental settings.

}, issn = {2041-1723}, doi = {10.1038/s41467-021-26942-0}, author = {Kurzthaler, Christina and Mandal, Suvendu and Bhattacharjee, Tapomoy and L{\"o}wen, Hartmut and Datta, Sujit S and Stone, Howard A} }