Chemical Engineering Seminar

Abstract:

Across the myriad lifeforms spanning biological scales from microns to meters, the two most profoundly influential, yet ubiquitously varying biological regulators that existed throughout the evolutionary process are oxygen availability and environmental mechanics. While diverse cellular processes such as metabolism, proliferation, motility, tumorigenesis, and fate decisions are affected by both varying oxygen availability and heterogeneous mechanical milieus, our present understanding of these processes is primarily shaped by independently interrogating the roles of either of these regulators without perturbing the other. Thus, an outstanding open question in contemporary biological sciences remains unanswered: how do combinatorial cues of oxygen partial pressure and microenvironment mechanics, an oxo-mechanical condition, regulate cellular state, and collective cellular organization? Our present work subjects cells to a combination of oxygen partial pressures and ECM densities - an oxo-mechanical cue - and investigates their morphology at the single cell level by combining morphometric measurements, bulk transcriptome analyses, as well as chemical modulation of intracellular mechanics and oxygen-driven signaling. At lower ECM densities, acute oxygen deprivation significantly alters cell morphology, whereas, at higher ECM densities, the effect of oxygen deprivation on cellular morphology is negligible. We independently show that a cell's response to varying oxygen availability depends on both substrate and intracellular mechanics; while the cell's engagement with mechanically diverse substrates is influenced by oxygen-driven signaling processes. Furthermore, we find that the combinatorial control of cellular morphology by oxygen availability and substrate mechanics is strikingly different in 2D vs 3D systems with identical viscoelastic properties and chemical composition. Together, our work identifies an oxo-mechanical regulation of cellular behavior in ECM-like contexts.

Biography:

Tapa is an Assistant Professor at the National Centre for Biological Sciences, Tata Institute of Fundamental Research in India. He completed his undergraduate studies at Jadavpur University and conducted his graduate work at the University of Florida. He was a Postdoctoral Fellow at the Andlinger Center for Energy and the Environment of Princeton University. 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.