Biology subjects

Hatzikirou, H.

Publications and source records attributed to Hatzikirou, H..

4 recordsLinked to original sources

bioRxiv2018

A least microenvironmental uncertainty principle (LEUP) as a generative model of collective cell migration mechanisms.

Collective migration is commonly observed in groups of migrating cells, in the form of swarms or aggregates. Mechanistic models have proven very useful in understanding collective cell migration. Such models, either explicitly consider the forces involved in the interaction and movement of individuals or phenomenologically define rules which mimic the observed behavior of cells. However, mechanisms leading to collective migration are varied and specific to the type of cells involved. Additionally, the precise and complete dynamics of many important chemomechanical factors influencing cell movement, from signalling pathways to substrate sensing, are typically either too complex or largely unknown. The question is how to make quantitative/qualitative predictions of collective behavior without exact mechanistic knowledge. Here we propose the least microenvironmental uncertainty principle (LEUP) that serves as a generative model of collective migration without incorporation of full mechanistic details. Interestingly we show that the famous Vicsek model is a special case of LEUP. Finally, as a proof of concept, we apply the LEUP to quantitatively study ofthe collective behavior of spherical Serratia marcescens bacteria, where the underlying migration mechanisms remain elusive.

biophysics↗

bioRxiv2018

Hook length of the bacterial flagellum is controlled to nanometer-scale for optimal motility performance

Most bacteria swim in liquid environments by rotating one or several flagella. The long external filament of the flagellum is connected to a membrane-embedded basal-body by a flexible universal joint, the hook, which allows the transmission of motor torque to the filament. The length of the hook is controlled on a nanometer-scale by a sophisticated molecular ruler mechanism. However, why its length is stringently controlled has remained elusive. We engineered and studied a diverse set of hook-length variants of Salmonella enterica. Measurements of plate-assay motility, single-cell swimming speed and directional persistence in quasi 2D and population-averaged swimming speed and body angular velocity in 3D revealed that the motility performance is optimal around the wild type hook-length. We conclude that too short hooks may be too stiff to function as a junction and too long hooks may buckle and create instability in the flagellar bundle. Accordingly, peritrichously flagellated bacteria move most efficiently as the distance travelled per body rotation is maximal and body wobbling is minimized. Thus, our results suggest that the molecular ruler mechanism evolved to control flagellar hook growth to the optimal length consistent with efficient bundle formation. The hook-length control mechanism is therefore a prime example of how bacteria evolved elegant, but robust mechanisms to maximize their fitness under specific environmental constraints.\n\nAuthor summaryMany bacteria use flagella for directed movement in liquid environments. The flexible hook connects the membrane-embedded basal-body of the flagellum to the long, external filament. Flagellar function relies on self-assembly processes that define or self-limit the lengths of major parts. The length of the hook is precisely controlled on a nanometer-scale by a molecular ruler mechanism. However, the physiological benefit of tight hook-length control remains unclear. Here, we show that the molecular ruler mechanism evolved to control the optimal length of the flagellar hook, which is consistent with efficient motility performance. These results highlight the evolutionary forces that enable flagellated bacteria to optimize their fitness in diverse environments and might have important implications for the design of swimming micro-robots.

microbiology↗

bioRxiv2017

Statistical mechanics of cell decision-making: the cell migration force distribution

Cell decision-making is the cellular process of responding to microenvironmental cues. This can be regarded as the regulation of cells intrinsic variables to extrinsic stimuli. Currently, little is known about the principles dictating cell decision-making. Regarding cells as Bayesian decision-makers under energetic constraints, I postulate the principle of least microenvironmental uncertainty (LEUP). This is translated into a free-energy principle and I develop a statistical mechanics theory for cell decision-making. I exhibit the potential of LEUP in the case of cell migration. In particular, I calculate the dependence of cell locomotion force on the steady state distribution of adhesion receptors. Finally, the associated migration velocity allows for the reproduction of the cell anomalous diffusion, as observed in cell culture experiments.

systems biology↗

bioRxiv2017

On The Principles Of Cell Decision-Making: Intracellular Coupling Improves Cell Responses Fidelity Of Noisy Signals

Reliability of cell fate decision-making is crucial to biological development. Until today it has not been clear what are biologys design principles that allow for reliable cell decision making under the influence of noise. Here, we attempt to answer this question by drawing an analogy between cell decision-making and information theory. We show that coupling of intracellular signalling pathway networks makes cell phenotypic responses reliable for noisy signals. As a proof of concept, we show how cis-interaction of the Notch-Delta pathway allows for increased performance under the influence of noise. Interestingly, in this case, the coupling principle leads to an efficient energy management. Finally, our postulated principle offers a compelling argument why cellular encoding is organized in a non-linear and non-hierarchical manner.

systems biology↗