@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 {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} }