Biology subjects

Malmi-Kakkada, A.

Publications and source records attributed to Malmi-Kakkada, A..

5 recordsLinked to original sources

bioRxiv2023

On the role of mechanical feedback in synchronous to asynchronous transition during embryogenesis

The initial stage of Zebrafish morphogenesis is characterized by a synchronous to asynchronous transition (SAT) in cell divisions. The cells divide in unison in the synchronous phase, unlike in the asynchronous phase. Despite the widespread observation of SAT in multiple organisms, there is no theoretical framework to predict the critical number of cell cycles n* that marks the beginning of asynchronous division. Here, by probabilistically modeling cell cycle progression under the assumption that the distribution of cell division times is broadened, we predict n* and the time at which the SAT occurs. The theory, supplemented by agent-based simulations, supports the hypothesis that the SAT emerges as a consequence of biomechanical feedback on cell division. Our results are in excellent agreement with the experiments while also explaining the cell cycle lengthening that arises as a result of biomechanical feedback. The emergence of the asynchronous phase is due to increasing fluctuations in the cell cycle times with each round of cell division. We also make several testable predictions that further sheds light on the role of biomechanical feedback in growing multicellular systems, such as during tissue and tumor growth.

biophysics↗

bioRxiv2023

Noise in the direction of motion determines the spatial distribution and proliferation of migrating cell collectives

A variety of living and non-living systems exhibit collective motion. From swarm robotics to bacterial swarms, and tissue wound healing to human crowds, examples of collective motion are highly diverse but all of them share the common necessary ingredient of moving and interacting agents. While collective motion has been extensively studied in non-proliferating systems, how the proliferation of constituent agents affects their collective behavior is not well understood. Here, we focus on growing active agents as a model for cells and study how the interplay between noise in their direction of movement and proliferation determines the overall spatial pattern of collective motion. In this agent-based model, motile cells possess the ability to adhere to each other through cell-cell adhesion, grow in size and divide. Cell-cell interactions influence not only the direction of cell movement but also cell growth through a force-dependent mechanical feedback process. We show that noise in the direction of a cells motion has striking effects on the emergent spatial distribution of cell collectives and proliferation. While higher noise strength leads to a random spatial distribution of cells, we also observe increased cell proliferation. On the other hand, low noise strength leads to a ring-like spatial distribution of cell collectives together with lower proliferation. Our findings provide insight into how noise in the direction of cell motion determines the local spatial organization of cells with consequent mechanical feedback on cell division impacting cell proliferation due to the formation of cell clusters.

biophysics↗

bioRxiv2021

Adhesion strength between cells regulate non-monotonic growth by a biomechanical feedback mechanism

We probe the interplay between intercellular interactions and pressure fluctuations associated with single cells in regulating cell proliferation using simulations of a minimal model for three-dimensional multicellular spheroid (MCS) growth. The emergent spatial variations in the cell division rate, that depends on the location of the cells within the MCS, is regulated by intercellular adhesion strength (fad). This in turn results in non-monotonic proliferation of cells in the MCS with varying adhesion strength, which accords well with experimental results. A biomechanical feedback mechanism coupling the fad and cell-dependent pressure fluctuations relative to a threshold value (pc) determines the onset of a dormant phase, and explains the non-monotonic proliferation response. Increasing fad from low values enhances cell proliferation because pressure on individual cells is smaller compared to pc. In contrast, at high fad, cells readily become dormant and cannot rearrange effectively, leading to arrested cell proliferation. Our work, which shows that proliferation is regulated by pressure-adhesion feedback loop, may be a general feature of tumor growth.

biophysics↗

bioRxiv2019

Generalized Rayleigh-Plesset Theory for Cell Size Maintenance in Viruses and Bacteria

The envelopes covering bacterial cytoplasm possess remarkable elastic properties. They are rigid enough to resist large pressures while being flexible enough to adapt to growth under environmental constraints. Similarly, the virus shells play an important role in their functions. However, the effects of mechanical properties of the outer shell in controlling and maintaining the sizes of bacteria or viruses are unknown. Here, we present a hydrodynamic "bubbles with shell" model, motivated by the study of bubble stability in fluids, to demonstrate that shell rigidity and turgor pressure control the sizes of bacteria and viruses. A dimensionless compliance parameter, expressed in terms of the Youngs modulus of the shell, its thickness and the turgor pressure, determines membrane response to deformation and the size of the organisms. By analyzing the experiment data, we show that bacterial and viral sizes correlate with shell elasticity, which plays a critical role in regulating size.

cell biology↗

bioRxiv2017

Cell growth rate dictates the onset of glass to fluid-like transition and long time super-diffusion in an evolving cell colony

Collective migration dominates many phenomena, from cell movement in living systems to abiotic self-propelling particles. Focusing on the early stages of tumor evolution, we enunciate the principles involved in cell dynamics and highlight their implications in understanding similar behavior in seemingly unrelated soft glassy materials and possibly chemokine-induced migration of CD8+ T cells. We performed simulations of tumor invasion using a minimal three dimensional model, accounting for cell elasticity and adhesive cell-cell interactions as well as cell birth and death to establish that cell growth rate-dependent tumor expansion results in the emergence of distinct topological niches. Cells at the periphery move with higher velocity perpendicular to the tumor boundary, while motion of interior cells is slower and isotropic. The mean square displacement, {Delta}(t), of cells exhibits glassy behavior at times comparable to the cell cycle time, while exhibiting super-diffusive behavior, {Delta}(t) {approx} t ( > 1), at longer times. We derive the value of {approx} 1.33 using a field theoretic approach based on stochastic quantization. In the process we establish the universality of super-diffusion in a class of seemingly unrelated non-equilibrium systems. Super diffusion at long times arises only if there is an imbalance between cell birth and death rates. Our findings for the collective migration, which also suggests that tumor evolution occurs in a polarized manner, are in quantitative agreement with in vitro experiments. Although set in the context of tumor invasion the findings should also hold in describing collective motion in growing cells and in active systems where creation and annihilation of particles play a role.

biophysics↗