Biology subjects

Pai, V.

Publications and source records attributed to Pai, V..

3 recordsLinked to original sources

bioRxiv2026

Purinergic signaling disrupts emergent patterns of multicellular coordination in basal Xenobots.

The ability of self-organizing systems to display emergent, adaptive capabilities is a fundamental feature of biological life. Understanding the mechanisms by which cells co-ordinate at the micro-scale to produce macro-scale structures and behaviors is a fundamental problem in developmental biology. Moreover, it is an important goal of biomedicine to identify triggers that re-wire the physiological patterns of information flow and control signals. Here, we use a recently developed, synthetic biology platform known as basal Xenobots to explore how patterns of information flow and multi-cellular integration are regulated by chemical signaling pathways. Basal Xenobots are modified, organoid-like systems constructed from embryos, and have previously been shown to display complex patterns of information flows. In this study, we recorded calcium signals before and after exposing basal Xenobots to extra-cellular adenosine triphosphate (eATP), and used statistics from multivariate information theory to explore the differences in global patterns of information flow across the cells in each state. We found that eATP resulted in a dramatic reconfiguration of global information processing dynamics, characterized by a global decrease in multi-cellular co-ordination, reduced information transfer and integration, and a decrease in the global entropy rate of the basal Xenobots. These results provide evidence that purinergic signaling may play a key role in the regulation of multi-cellular self-organization, with implications for a variety of clinical disorders thought to involve aberrant purinergic signaling. These results also suggest the possibility that bioengineers may be able to "tune" the degree of self-organizing capacity in living systems via pharmacological intervention.

systems biology↗

bioRxiv2026

Ionic Regulation of Mechanosurveillance and Metastasis via the MRTFA/KCNMB1 Axis

Cellular stiffness profoundly impacts cancer metastasis at multiple levels, but mechanisms that regulate cancer cells stiffness remain poorly understood. Here, we identified potassium efflux and KCNMB1, an auxiliary subunit of the large conductance potassium efflux (BK) channels, as regulators of cellular stiffness downstream of myocardin related transcription factor A (MRTFA). In primary pericytes, KCNMB1 knockdown increased cellular stiffness, which is consistent with the role of potassium efflux in promoting relaxation during excitation-contraction coupling. In a striking contrast, however, KCNMB1 knockdown decreased cellular stiffness in cancer cells. Softer cancer cells were resistant to NK cell mediated cytotoxicity and the low KCNMB1 expression was associated with worse survival in breast cancer patients. Importantly, pharmacological activation of BK channels reduced metastatic burden in mice and improved lysis of cancer cells by cytotoxic T-lymphocytes. These results highlight the unique ionic regulation of stiffness in cancer cells and point to BK channel agonism as a new therapeutic approach in cancer.

cancer biology↗

bioRxiv2024

Identification of brain-like functional information architectures in embryonic tissue of Xenopus laevis.

Understanding how populations of cells collectively coordinate activity to produce the complex structures and behaviors that characterize multicellular organisms, and which coordinated activities, if any, survive processes that reshape cells and tissues into organoids, are fundamental issues in modern biology. Here we show how techniques from complex systems and multivariate information theory provide a framework for inferring the structure of collective organization in non-neural tissue. Many of these techniques were developed in the context of theoretical neuroscience, where these statistics have been found to be altered during different cognitive, clinical, or behavioral states, and are generally thought to be informative about the underlying dynamics linking biology to cognition. Here we show that these same patterns of coordinated activity are also present in the aneural tissues of evolutionarily distant biological systems: preparations of embryonic Xeno-pus laevis tissue (known as "basal Xenobots"). These similarities suggest that such patterns of activity either arose independently in these two systems (epithelial constructs and brains); are epiphenomenological byproducts of other dynamics conserved across vastly different configurations of life; or somehow directly support adaptive behavior across diverse living systems. Finally, these results provide unambiguous support for the hypothesis that, despite their apparent simplicity as collections of non-neural epithelial cells, Xenobots are in fact integrated, complex systems in their own right, with sophisticated internal information structures.

systems biology↗