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Biology subjects

Dalwadi, M. P.

Publications and source records attributed to Dalwadi, M. P..

5 recordsLinked to original sources

A dynamical analysis of the alignment mechanism between two interacting cells

In this work we analytically investigate the alignment mechanism of self-propelled ellipse-shaped cells in two spatial dimensions interacting via overlap avoidance. By considering a two-cell system and imposing certain symmetries, we obtain an analytically tractable dynamical system, which we mathematically analyse in detail. We find that for elongated cells there is a half-stable steady state corresponding to perfect alignment between the cells. Whether cells move towards this state (i.e. become perfectly aligned) or not is determined by where in state space the initial condition lies. We find that a separatrix splits the state space into two regions, which characterise these two different outcomes. We find that some self-propulsion is necessary to achieve perfect alignment, however too much self-propulsion hinders alignment. Analysing the effect of small amounts of self-propulsion offers an insight into the timescales at play when a trajectory is moving towards the point of perfect alignment. We find that the two cells initially move apart to avoid overlap over a fast timescale, and then the presence of self-propulsion causes them to move towards a configuration of perfect alignment over a much slower timescale. Overall, our analysis highlights how the interaction between self-propulsion and overlap avoidance is sufficient to generate alignment.

biophysics↗

Pattern formation along signaling gradients driven by active droplet behaviour of cell groups

Gradients of extracellular signals organise cells in tissues. Although there are several models for how gradients can pattern cell behaviour, it is not clear how cells react to gradients when the population is undergoing 3D morphogenesis, in which cell-cell and cell-signal interactions are continually changing. Dictyostelium cells follow gradients of their nutritional source to feed and maintain their undifferentiated state. Using light sheet imaging to simultaneously monitor signaling, single cell and population dynamics, we show that the cells migrate towards nutritional gradients in swarms. As swarms advance, they deposit clumps of cells at the rear, triggering differentiation. Clump deposition is explained by a physical model in which cell swarms behave as active droplets: cells proliferate within the swarm, with clump shedding occurring at a critical population size, at which cells at the rear no longer perceive the gradient and are not retained by the emergent surface tension of the swarm. The droplet model predicts vortex motion of the cells within the swarm emerging from the local transfer of propulsion forces, a prediction validated by 3D tracking of single cells. This active fluid behaviour reveals a developmental mechanism we term "musical chairs" decision-making, in which the decision to proliferate or differentiate is determined by the position of a cell within the group as it bifurcates.

biophysics↗

Motility-Induced Phase Separation Mediated by Bacterial Quorum Sensing

We study motility-induced phase separation (MIPS) in living active matter, in which cells interact through chemical signalling, or quorum sensing. In contrast to previous theories of MIPS, our multiscale continuum model accounts explicitly for genetic regulation of signal production and motility. Through analysis and simulations, we derive a new criterion for the onset of MIPS that depends on features of the genetic network. Furthermore, we identify and characterise a new type of oscillatory instability that occurs when gene regulation inside cells promotes motility in higher signal concentrations.

biophysics↗

Universal dynamics of biological pattern formation in spatio-temporal morphogen variations

In biological systems, chemical signals termed morphogens self-organise into patterns that are vital for many physiological processes. As observed by Turing in 1952, these patterns are in a state of continual development, and are usually transitioning from one pattern into another. How do cells robustly decode these spatio-temporal patterns into signals in the presence of confounding effects caused by unpredictable or heterogeneous environments? Here, we answer this question by developing a general theory of pattern formation in spatio-temporal variations of pre-pattern morphogens, which determine gene-regulatory network parameters. Through mathematical analysis, we identify universal dynamical regimes that apply to wide classes of biological systems. We apply our theory to two paradigmatic pattern-forming systems, and predict that they are robust with respect to non-physiological morphogen variations. More broadly, our theoretical framework provides a general approach to classify the emergent dynamics of pattern-forming systems based on how the bifurcations in their governing equations are traversed.

biophysics↗

Emergent robustness of bacterial quorum sensing in fluid flow

Bacteria use intercellular signaling, or quorum sensing (QS), to share information and respond collectively to aspects of their surroundings. The autoinducers that carry this information are exposed to the external environment; consequently, they are affected by factors such as removal through fluid flow, a ubiquitous feature of bacterial habitats ranging from the gut and lungs to lakes and oceans. To understand how QS genetic architectures in cells promote appropriate populationlevel phenotypes throughout the bacterial life cycle requires knowledge of how these architectures determine the QS response in realistic spatiotemporally varying flow conditions. Here, we develop and apply a general theory that identifies and quantifies the conditions required for QS activation in fluid flow by systematically linking cell- and population-level genetic and physical processes. We predict that, when a subset of the population meets these conditions, cell-level positive feedback promotes a robust collective response by overcoming flow-induced autoinducer concentration gradients. By accounting for a dynamic flow in our theory, we predict that positive feedback in cells acts as a low-pass filter at the population level in oscillatory flow, allowing a population to respond only to changes in flow that occur over slow enough timescales. Our theory is readily extendable, and provides a framework for assessing the functional roles of diverse QS network architectures in realistic flow conditions.

biophysics↗