Physico-chemical regulation of living matter across scales

ORAL

Abstract

How physical environments regulate lifeforms remains an extensively explored, yet perpetually intriguing question. My PhD research pioneers a new perspective which establishes the physical microenvironment as an active regulator of living matter across scales. Towards this, we have innovated bioengineered 3D culture platforms that mimic the spatial architecture of habitats such as soil, mucus, and tissues. Leveraging these, we have explored how biophysical constraints regulate growth, motility, morphology, and cellular states across scales, viz., demonstrating that 3D confinement acts as a potent selective pressure on bacterial communities; discovering a fundamentally unique mode of physical control over cell cycle progression in budding yeast; establishing how viscoelastic regimes govern transitions in worm motility; characterizing environmental cues which regulate the organization and plasticity of structurally-heterogeneous ovarian cancer spheroids; and identifying that the cellular state is an emergent property resulting from a unique regulatory axis between oxygen signalling and mechanical regimes. Together, our work pioneers generalizable principles describing the physical regulation of biological phenomena across complex 3D microenvironments.

*National Centre for Biological Sciences. Grant Number: Intramural funding

Publication: Published papers:
1. M Sreepadmanabh, M. Ganesh, P. Sanjebam, C. Kurzthaler, D. Agashe, and T. Bhattacharjee - Cell shape affects bacterial colony growth under physical confinement; Nature Communications (2024)
2. M Sreepadmanabh, M. Ganesh, J. Langthasa, R. Bhat, and T. Bhattacharjee - Distinct chemical cues reprogram cellular and multicellular phenotypes in ovarian cancer spheroids; Small (2025)
3. M Sreepadmanabh, M. Ganesh, R. Bhat, and T. Bhattacharjee - Jammed microgel growth medium prepared by flash-solidification of agarose for 3D cell culture and 3D bioprinting; Biomedical Materials (2023)
4. M Sreepadmanabh*, A. B. Arun*, and T. Bhattacharjee - Design approaches for 3D cell culture and 3D bioprinting platforms; Biophysics Reviews (2024)

Preprints:
5. M Sreepadmanabh*, M. Gautam*, N. Bagade, S. Laxman, and T. Bhattacharjee - 3D confinement physically regulates cell cycle progression in budding yeast; bioRxiv (2025)
6. M Sreepadmanabh*, S. Dey*, S. Kundu, A. B. Arun, S. P. Koushika, S. Thutupalli, D. Hewitt, T. Bhattacharjee# - Physical confinement regulates transition in nematode motility; bioRxiv (2025)

Planned papers:
7. M Sreepadmanabh, N. Hariharan, D. Palakodeti, and T. Bhattacharjee# - An oxo-mechanical regulation of cellular morphology in 3D (in preparation)
8. S. Thomas*, M Sreepadmanabh*, A. Puzhakkal, V. Srivastava, T. Bhattacharjee, and A. Redkar - A transparent soil-like 3D matrix for studying plant-fungal interactions (in preparation)

Presenters

  • M Sreepadmanabh

    • National Center for Biological Sciences
    • National Centre For Biological Sciences (TIFR)

Authors

  • M Sreepadmanabh

    • National Center for Biological Sciences
    • National Centre For Biological Sciences (TIFR)
  • Tapomoy Bhattacharjee

    • Tata Institute of Fundamental Research (TIFR)
    • National Centre For Biological Sciences (TIFR)