MechE Seminar Series: Tapomoy Bhattacharjee

Speaker: Dr. Tapomoy Bhattacharjee

Title: Physical regulation of cellular growth by 3D confinement

Abstract: The natural habitats of most microbes are complex 3D environments with spatiotemporally dynamic material properties which exerts a physical constraint on fundamental biological processes such as growth. However, our current knowledge of cellular biology largely derives from experiments performed using either homogeneously mixed liquid broths or flat surfaces, neither of which recapitulate the complex mechanical architecture inherent in physiological niches. We bridge this gap by engineering mechanically tunable transparent 3D porous media which mimic both the pore-scale architecture and viscoelastic properties of diverse biological habitats. Using this, we explore how the mechanical microenvironment fundamentally alters cellular growth at both the population and single-cell level. Working with bacterial cells, we combine computational modelling, experiments, and competitive co-cultures to find that high-aspect ratio bacteria outperform low-aspect ratio bacteria under elevated physical confinement by leveraging efficient 3D colony architecture to enhance nutrient accessibility. These findings establish that 3D confinement selectively confers cell shape-dependent growth advantages translating to a population-level competitive advantage. Hence, our work implicates that physical confinement as a potent selective pressure on bacterial communities. Further, using budding yeast model we investigate how 3D physical confinement affects growth at the single-cell level. Surprisingly, while we observe a clear confinement-dependent alteration of proliferation rates without any growth defects, we do not detect any transcriptional signatures associated with canonical mechanosensation or stress signalling. Rather, robust biophysical characterizations suggest that the process of budding is physically constrained by 3D confinement, manifesting as a delayed progression through the cell cycle. This provides a remarkable demonstration of purely physical control over cell division—a highly conserved and synchronized biological process – without invoking biochemical regulatory modules. Together, our findings point towards a fundamentally unique form of physical regulation over cellular growth, which is centrally mediated by the constraints imposed by a cell’s local surroundings.

About the Speaker: Tapa is an Assistant Professor at the National Centre for Biological Sciences, Tata Institute of Fundamental Research in India. He is also elected as the young investigator of the European Molecular Biology Organization. Tapa completed his undergraduate studies at Jadavpur University and conducted his graduate work at the University of Florida where he worked with Prof. Tommy Angelini. His Ph.D. work involved inventing embedded bioprinting and 3D cell culture methods using microgels. He was a Postdoctoral Fellow at the Andlinger Center for Energy and the Environment of Princeton University where he worked with Prof. Sujit Datta. At Princeton Tapa discovered the hopping and trapping dynamics of bacteria in porous media. Currently, Tapa’s lab focuses on understanding growth, motility, and mechanics across different scales in three-dimensional media. His lab also studies the combinatorial effect of different environmental cues on cellular behavior.