Spatial Organization of Biological Fuctions | BPS Thematic Meeting

Spatial Organization of Biological Functions Meeting

Thursday Speaker Abstracts

AN OXO-MECHANICAL REGULATION OF CELL STATE Sreepadmanabh M 1 ; Nivedita Hariharan 2 ; Dasaradhi Palakodeti 2 ; Tapomoy Bhattacharjee 1 ; 1 National Centre for Biological Sciences, Bengaluru, India 2 Institute For Stem Cell Science and Regenerative Medicine, Bengaluru, India Across the myriad lifeforms spanning biological scales from microns to meters, the two most profoundly influential, yet ubiquitously varying biological regulators 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 is primarily shaped by independently interrogating the roles of either of these regulators without perturbing the other. Thus, a critical question remains unanswered: how do combinatorial inputs of oxygen partial pressures and microenvironment mechanics regulate cellular state? Our present work subjects cells to a combination of oxygen partial pressures and ECM densities - an oxo-mechanical cue - and profiles the cellular state by combining biophysical morphometrics, bulk transcriptome analyses, as well as chemical modulation of intracellular mechanics and oxygen-driven signaling. At lower ECM densities, acute oxygen deprivation significantly alters the cellular state, whereas, at higher ECM densities, the effect of oxygen deprivation 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. Finally, using ATAC-Seq, we show that substrate mechanics alters the global chromatin accessibility, which allows hypoxic dysregulation to profoundly manifest specifically in low ECM density environments - providing a mechanistic basis for oxo-mechanical effects. Together, our work identifies an oxo-mechanical regulatory paradigm governing cellular behavior in 3D ECM-like contexts.

MORPHOGEN AND BOUNDARY PATTERNING IN DEVELOPING SYSTEMS Timothy Saunders University of Warwick, United Kingdom No Abstract

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