Research Projects

Cells undergo volume adjustments in various physiological and non-physiological states, causing undesirable shifts in macromolecular crowding (MMC), plasma membrane tension, and ionic concentration. To avoid these negative effects, cells initiate volume regulation via osmosis-driven water exchange. The molecular mechanism of cell volume sensing and triggering volume-regulatory apparatus is poorly understood. Cell volume control is associated with key functions such as cell-cycle regulation, migration, differentiation, and apoptosis. Despite poor consensus, many hypotheses suggest autonomous regulation of cell volume. Conflicting results suggest that the nature of volume sensing must be global factors like MMC, membrane-tension driven signaling, and cytoplasmic ROS. The high density of proteins in cytoplasmic macromolecules, which constitute 57% of them, creates a condition of MMC, which globally influences the biochemistry in the cytoplasm. The MMC and volume of the cytoplasm are inversely related, making MMC a potential sensor of volume change. However, there is no direct evidence to establish this, primarily due to the lack of suitable methods to monitor MMC in live cells accurately. This proposal aims to dissect different factors such as MMC, ROS, and membrane tension-dependent activity of TNFR1 in cell volume regulation, explore the nature of MMC in cell cytoplasm, and investigate whether volume homeostasis depends on the physical makeup of the extracellular microenvironment.